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| ABSTRACT |
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| Year : 2018 | Volume
: 33
| Issue : 5 | Page : 31-113 |
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Abstracts
| Date of Web Publication | 9-Nov-2018 |
Correspondence Address:
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
. Abstracts. Indian J Nucl Med 2018;33, Suppl S1:31-113 |
 Cardiology Track | |  |
| OP1: Dyssynchrony evaluation using NH3 cardiac positron emission tomography in asymptomatic diabetic patients compared to age-matched healthy controls with low risk of coronary artery disease | | |
Vankadari Kousik, Ashwani Sood, Anish Bhattacharya, Bhagwant Rai Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Background and Objectives: Dyssynchrony refers to abnormal myocardial activation leading to inhomogenous contraction of the left ventricular (LV) muscle fibers and reduced LV ejection fraction. The role of LV mechanical dyssynchrony assessment with gated single-photon emission computed tomography in selection and response assessment of patients, who undergo cardiac resynchronization therapy, is widely discussed. Recently, there is emerging evidence to assess the role of dyssynchrony in identifying asymptomatic diabetic patients who may develop diabetic cardiomyopathy. This study aims to evaluate LV mechanical dyssynchrony with N-13 labeled NH3 positron emission tomography (PET) in asymptomatic diabetic patients (>3 years) compared to age-matched healthy controls. Materials and Methods: We retrospectively analyzed 124 patients aged 30–78 years who underwent 1 day stress/rest N-13 labeled NH3 cardiac PET from December 2015 to July 2018. Among them, 33 patients aged 40–70 years (21 males, 12 females) with asymptomatic type II diabetes, absence of obesity, and other comorbidities underwent N-13-labeled NH3 cardiac PET. Twenty-eight patients (12 males, 16 females) aged 39–72 years with the absence of diabetes, obesity, and low risk for coronary artery disease who underwent N-13 labeled NH3 cardiac PET were taken as controls. LV dyssynchrony assessment was done using phase analysis with Corridor 4DM software. Phase standard deviation (PSD) and histogram bandwidth (HBW) were recorded from phase histogram in both rest and stress PET images in all the patients included in our study. The statistical significance of the dyssynchrony parameters (PSD and HBW) in asymptomatic diabetics versus normal healthy controls was assessed using the Mann–Whitney test. Results: The mean PSD and HBW of resting study were significantly higher in diabetic patients compared to nondiabetic healthy controls (PSD = 28 vs. 15.4, P = 0.01) (HBW = 100 vs. 62.2, P = 0.01). Mean PSD and mean HBW of stress study were also significantly higher in patients with asymptomatic diabetes compared to normal nondiabetic controls (PSD = 25.2 vs. 14.7, P = 0.01) (HBW = 98.6 vs. 58.6, P = 0.009). Conclusion: Our findings indicate that asymptomatic diabetic patients have significant dyssynchrony compared to normal healthy nondiabetic controls and dyssynchrony on phase analysis with cardiac PET can be used to predict diabetic cardiomyopathy.
| OP2: Role of 68Ga-DOTANOC positron emission tomography/computed tomography and myocardial perfusion imaging in cardiac sarcoidosis: A comparison to cardiac magnetic resonance | | |
Prateek Kaushik, Chetan D. Patel, Rajiv Kumar, Gurpreet Singh Gulati1, Neeraj Parakh2, Sandeep Seth2, Randeep Guleria3, C. S. Bal
Departments of Nuclear Medicine, 1Cardiac Radiology, 2Cardiology and 3Pulmonary Medicine, AIIMS, New Delhi, India
Background and Objectives: Cardiac sarcoidosis is an uncommon, but potentially fatal manifestation of sarcoidosis characterized by granulomatous inflammation, leading to myocardial fibrosis. There is no gold standard test for diagnosis, and a combination of clinical criteria, cardiac magnetic resonance (CMR), and nuclear imaging procedures is used to detect cardiac involvement. Nuclear medicine imaging for cardiac sarcoidosis involves a combination of myocardial perfusion imaging (MPI) to identify fibrosis and 18F-labeled fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to detect active inflammation associated with the disease. However, the utility of 18F-FDG PET is limited by inadequate suppression of physiological myocardial uptake in all patients. Recently, 68Ga-DOTANOC has emerged as a useful alternative PET tracer for imaging inflammation as it targets somatostatin receptors expressed on inflammatory cells and does not show physiological myocardial uptake. The aim of our study was to use MPI and 68Ga-DOTANOC PET/CT in patients suspected of cardiac sarcoidosis and to compare the results with cardiac magnetic resonance imaging (MRI). Materials and Methods: Fifteen patients with clinical suspicion of cardiac sarcoidosis underwent cardiac MRI, MPI with 99mTc-MIBI, and 68Ga-DOTANOC PET/CT. Images were read by a cardiac radiologist and a nuclear medicine physician and reported as positive or negative for cardiac sarcoidosis. Considering CMR as gold standard, sensitivity, specificity, PPV, and NPV were calculated for the combination of MPI and 68Ga-DOTANOC. Results: There were 13 male and two female patients (mean age: 39.1 years). Three patients had normal perfusion and no abnormal uptake on 68Ga-DOTANOC scan. Five patients had normal perfusion with abnormal 68Ga-DOTANOC uptake. Seven patients had perfusion defects and abnormal uptake on 68Ga-DOTANOC PET/CT. Cardiac MRI was suggestive of sarcoidosis in 11 patients. Considering CMR as gold standard, the combination of 68Ga-DOTANOC and MPI had a sensitivity and specificity of 100% and 75%, respectively, and PPV and NPV of 91.6% and 100%, respectively. Conclusion: A combination of MPI and 68Ga-DOTANOC PET/CT has high sensitivity and specificity in patients with suspicion of cardiac sarcoidosis. Nuclear imaging can also be useful in patients in whom CMR is contraindicated. Since 68Ga-DOTANOC PET/CT imaging detects inflammation, it can potentially be used to monitor disease activity and response to treatment.
| OP3: Evaluation of cardiac sympathetic denervation using L-3,4-dihydroxy-6-F-18fluorodihydroxyphenylalanine-positron emission tomography-computed tomography in Parkinson disease | | |
Harish Goyal, Chandra Sekhar Bal, Chetan D. Patel, Vinay Goyal, Madhavi Tripathi, Priyanka Gupta, Praveen Kumar
Department of Nuclear Medicine, All India Institutes of Medical Sciences, New Delhi, India
Background and Objectives: We evaluated myocardial sympathetic innervation using L-3,4-dihydroxy-6-F-18fluorodihydroxyphenylalanine (18F-FDOPA) PET-CT in idiopathic Parkinson's disease (IPD) patients and atypical Parkinsonian disorder (APD) patients. Materials and Methods: This study prospectively evaluated 18F-FDOPA positron emission tomography-computed tomography (PET-CT) cardiac images of 86 IPD and APD patients referred for routine dopaminergic imaging for movement disorder after undergoing a detailed clinical examination. The clinical diagnosis was based on unified Parkinson disease rating scale (UPDRS) and Hoehn and Yahr (H&Y) scale. These included 64 IPD patients (28 early IPD [age = 54 ± 9.8 years; UPDRS = 37.3 ± 12.2; H&Y <2.0, disease duration = 4.2 ± 3.4 years] and 39 advanced IPD [age = 60 ± 8.5 years; UPDRS = 52.3 ± 8.4; H&Y = 2.0–4.0, disease duration = 9.6 ± 5.2 years]) along with 19 patients with APD (age = 60 ± 12.5 years). Autonomic dysfunction was assessed by autonomic function tests to evaluate neurocirculatory failure. We also evaluated 32 age-matched controls who had undergone 18F-FDOPA PET-CT for indication other than Parkinsonism and had no history of coronary artery disease or coronary risk factors. All the subjects underwent 18F-FDOPA cardiac PET-CT study. Cardiac images were interpreted visually and semi-quantitatively using SUVmax value. We derived global myocardium-to-liver ratio (MLR) and myocardium-to-mediastinal vessel ratio (MMR).The values of MMR and MLR derived from controls were compared with IPD and APD patient groups using unpaired t-test. The study was approved by the institutional ethical committee and informed consent was obtained. Results: The mean global MLR in controls, early IPD patients, and advanced IPD patients was 2.64 ± 0.69, 2.28 ± 0.42, 1.43 ± 0.59, respectively. Moreover, the mean global MMR in controls, early IPD patients, and advanced IPD patients was 4.64 ± 1.17, 3.44 ± 0.89, 2.63 ± 0.86, respectively. The mean global MLR and MMR in APD patients were 2.72 ± 0.79 and 4.49 ± 1.08, respectively. We compared these ratios between controls and subjects with IPD subgroups and APD group separately. The difference was found to be statistically significant in control group and advanced IPD subgroup (P = 0.001). There was statistically significant difference between early IPD and APD subgroup (P = 0.017), but no significant difference was noted between control and APD subgroup (P = 0.706). Conclusion: FDOPA PET-CT can be used to evaluate myocardial sympathetic denervation in patients of advanced IPD and can differentiate Parkinsonism phenotypes.
| PP1: Stress myocardial perfusion single-photon emission computed tomography in patients with knee osteoarthritis before knee replacement surgery | | |
N. Satish, C. Piyush, G. Chandran, A. Manikandan, P. Sarvannan
MIOT International, Chennai, Tamil Nadu, India
Background and Objectives: Implicating physical inactivity, advanced age, and cardiovascular risk factors, studies have shown a higher incidence of ischemic heart disease in patients with knee osteoarthritis (OA). In this study, we aimed to test this association in this subgroup of clinically asymptomatic patients before them undergoing knee replacement surgeries. Materials and Methods: This is a retrospective analysis of all patients (from December 2016 to June 2018) who were referred for preoperative evaluation before undergoing total knee replacement surgery. Patients with prior a history of any cardiac events were excluded from the study. Pharmacological stress myocardial perfusion imaging (MPI) was done using intravenous adenosine (n = 80) or dobutamine infusion (n = 5). Hypoperfusion was graded mild, moderate, or severe, and size of the defect was small, medium, or large depending upon whether <5%, 5%–10%, or >10% of the myocardium was involved, respectively. Results: Of the 101 patients referred for stress MPI, 16 were excluded (as they had prior known ischemic heart disease/events) and final analysis was done in 85 patients. Mean age of the patients was 64 years (range 48–85), males was 28 years, and female was 57 years. Forty-three percent were aged above 65 years, 41% of the patients had diabetes, 54% were hypertensive, and 29% have both diabetes and hypertension. Abnormal stress MPI scans were seen in 34% (n = 29/85). Of these abnormal MPI scans, small-sized/mild ischemia was noted in 82% (n = 24/29), medium-sized moderate ischemia in 13% (n = 4/29), large-sized severe ischemia in 3% (n = 1/29). Affected vascular territory was left anterior descending territory in 48% (14/29), left circumflex artery territory in 34% (n = 10/29), and right coronary artery territory in 17% (n = 5/29). Higher incidence of abnormal scans was seen in patient having diabetes (relative risk [RR] 1.33), hypertension (RR 1.88), or patients having both diabetes/hypertension (RR 2.32), age >65 (RR 1.33), and male gender (RR 1.24). There were no adverse events noted in any patients subjected to the pharmacological stress. Conclusion: Almost a third of the patient with knee OA have subclinical myocardial ischemia when evaluated using pharmacological stress MPI before undergoing joint replacement surgeries. Further assessment with along with coronary angiographic correlation would be needed to demonstrate the impact of identifying subclinical ischemia in this subgroup of patients on clinical decision-making and perioperative and long-term outcomes.
| PV1: Impact of reconstruction algorithms in measurement of ejection fraction on myocardial perfusion scan | | |
Suman Manohar, Madhusudhanan Ponnusamy
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Objectives: Gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been widely used to evaluate patients with ischemic heart disease. Iterative reconstruction algorithm is superior to filtered back projection in myocardial perfusion SPECT. Recent advances in iterative reconstruction are collimator response recovery, which is incorporated in different software like Flash 3D. Myocardial perfusion scan provides useful information regarding perfusion and left ventricular function. Echo is the most common preliminary investigation used to assess left ventricular function. Left ventricle ejection fraction (EF) is one of the important parameters used in assessing cardiac function. We compared EF measured by echocardiography, 2D OSEM, and Flash 3D. Materials and Methods: We retrospectively evaluated 44 patients, who had undergone 99mTc MIBI-gated stress myocardial perfusion study between May 2018 and July 2018. Images were acquired on a dual-headed SPECT/CT from right anterior oblique to left posterior oblique, 64 projections of 20-s duration. Images were reconstructed using both 2D OSEM and 3D OSEM (Flash 3D, Siemens) and EF was calculated using 4DM SPECT software. Paired t-test was used for comparison of EFs measured by the two reconstruction algorithms and EF measured by echocardiography. Results: Mean EF measured by 2D OSEM, Flash 3D, and echocardiography were 64.1 (standard deviation [SD] 19.43), 63.65 (SD 20.2), and 53.57 (SD 11.26), respectively. There was a significant difference between EF values measured by either 2D OSEM or Flash 3D and echocardiography (P = 0.001). However, no significant difference was obtained between EF measured by 2D OSEM and Flash 3D (P = 0.70). Conclusion: Reconstruction algorithm does not have much impact on the EF values measured on gated myocardial perfusion scan. Therefore, 3D OSEM algorithm that provides better image quality even with lower count density images may be used to generate EF values in routine practice.
| PV2: Role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in diagnostically challenging cases of infective endocarditis: An institutional experience | | |
Bushra Asima
Department of Nuclear Medicine, Army Hospital, R and R, New Delhi, India
Background and Objectives: The aim of the study was to essay the role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) in the evaluation of diagnostically challenging cases of infective endocarditis, particularly prosthetic valve endocarditis. Infective endocarditis is widely underdiagnosed or diagnosed after a major delay. Diagnosis remains a challenge especially in patients with an implantable cardiac device. Timely diagnosis of infective endocarditis is very important. The detection of clinically relevant foci of infection is very crucial for appropriate treatment regimens and surgical intervention. Materials, Methods, and Results: A prospective, observational study conducted at Army Hospital R and R over 2 years from August 2016 to August 2018. The study comprised 12 patients with suspected infective endocarditis. The patients included were those who completed a diagnostic workup including clinical evaluation, blood cultures, and echocardiography. Whole-body 18FDG PET-CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. Results were analyzed. Conclusion: PET-CT identified five cases of infective endocarditis.
| PV3: Evaluation of stress-induced left ventricular mechanical dyssynchrony using gated single-photon emission computed tomography myocardial perfusion scintigraphy | | |
B Prasanth, H. V. Sunil
Department of Nuclear Medicine and PET/CT, Narayana Hrudayalaya, Bengaluru, Karnataka, India
Objective: The purpose of this study was to use 99mTc sestamibi-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to detect the presence of stress-induced left ventricular mechanical dyssynchrony (LVMD). Materials and Methods: Ninety-seven patients who were referred for exercise stress and rest 99mTc sestamibi-gated SPECT MPI were enrolled in this study. Remaining images were acquired after 60 min of tracer injection. Stress images were acquired after 5–10 min of exercise stress MPI. The patients were divided into three groups: normal group (n = 31), ischemia group (n = 33), and infarct group (n = 31) based on perfusion pattern. LV dyssynchrony parameters were calculated by phase analysis and compared the stress and rest images across the three groups. Results: LVMD parameters were larger during stress than during rest in all the three groups; however, in the ischemia group, LV dyssynchrony was significantly larger poststress than at rest. As the severity and extent of ischemia increase, there was more worsening of stress-induced LVMD. Conclusion: The different dyssynchrony patterns between normal, ischemic, and infarcted myocardium were evaluated. LVMD changes early poststress may aid the diagnosis of coronary artery disease using 99mTc-gated SPECT MPI. Stress-induced myocardial ischemia caused more dyssynchronous contraction in the ischemic region, leading to deterioration in LV synchrony. As the severity and extent of ischemia increase, there is more worsening of stress-induced LVMD.
| Endocrinology Track | | |
| OP4: Utility of 68-Ga EXENDIN-4 and 68-Ga-DOTATATE positron emission tomography-computed tomography in the evaluation/management of hypoglycemic syndromes | | |
G. Dinesh Kumar, Vikram Lele, Rajlaxmi Jagtap, Pankaj Kumar, Karuna Luthra
Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Investigation of nondiabetic hypoglycemic syndromes include the use of a variety of cellular targets such as peptide receptors – somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptor (GLP-1R), the amine precursor uptake and decarboxylation system utilizing the dihydroxyphenylalanine (DOPA) analog 6-[18F]-l-?uoro-l-3,4-DOPA, and glycolytic metabolism with 2-[18F]?uoro-2-deoxy-d-glucose (FDG). Benign insulinoma has a dense expression of GLP-1R, whereas malignant insulinoma has SSTR expression. FDG may be helpful in assessing higher grades of malignant insulinoma. Thus, a spectrum of differentiation is seen in the expression of following tracers, with GLP-1R > SSTR > FDG in benign insulinoma and the opposite in higher-grade disease. This has been described as TRIPLE-FLOP phenomenon1. Our objective was to localize insulin-secreting tumors with both 68-Ga EXENDIN-4 and 68-Ga DOTATATE positron emission tomography-computed tomography (PET-CT). Materials and Methods: We studied patients who were referred to our institute for evaluation of hypoglycemia. The patients who presented with Whipple's triad for hypoglycemia (symptomatic fasting hypoglycemia, blood glucose level <50mg/dL, with relief of symptoms after administration of glucose) were evaluated. 68-Ga EXENDIN-4 and 68-Ga DOTATATE PET-CT were performed on separate days with dedicated 16 slice PET-CT (GE–Discovery IQ 5 ring scanner). Standard uptake values normalized to body weight were obtained over lesions. The patients were followed up for their surgical and glycemic control status. Results: We present data of five patients, in whom we evaluated seven lesions in the pancreas of four patients. Heterogeneity was noted between EXENDIN-4 and DOTATATE uptake in these lesions. Three of seven lesions were positive only for DOTATATE, whereas two of seven were positive only for EXENDIN-4. Two lesions were congruent, showing both EXENDIN-4 and DOTATATE uptake. One of the patients was a known case of MEN1 syndrome, who had four lesions (multicenter insulinomas) and had heterogeneity in tracer uptake over the lesions. On follow-up, these four patients underwent surgical intervention and attained euglycemic status. The fifth patient in whom only EXENDIN PET-CT was performed showed diffuse tracer uptake in bulky pancreas and diagnosed as noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Conclusion: 68-Ga EXENDIN-4 and 68-Ga DOTATATE PET-CT should be used synergistically for evaluation of multicenter insulinomas in MEN-1 syndrome patients. 68-Ga DOTATATE negative sporadic insulinomas should be evaluated with 68-Ga EXENDIN-4 PET-CT for localization, in view of high GLP-1R density on benign insulinomas (TRIPLE-FLOP phenomenon). 68-Ga EXENDIN-4 PET-CT is also useful for imaging NIPHS.
| OP5: Role of 18F-DOPA positron emission tomography/computed tomography in children with persistent hyperinsulinemic hypoglycemia | | |
K. Sreenivasa Reddy, Nishikant Avinash Damle, Harish Goyal, Geetanjali Arora, Rajni Sharma1, Vandana Jain1, Madhavi Tripathi, Shamim Ahmed Shamim, Rakesh Kumar, Chandra Sekhar Bal
Departments of Nuclear Medicine and 1Pediatrics, AIIMS, New Delhi, India
Background and Objective: Persistent hyperinsulinemic hypoglycemia is a rare, but life-threatening disease of infancy and childhood. 18F-DOPA positron emission tomography/computed tomography (PET/CT) has been shown to be a useful modality in the localization of culprit pancreatic lesions in these patients. We aimed to assess the role of 18F-DOPA PET/CT in such patients at our institution. Materials and Methods: 18F-DOPA PET/CT scans and clinical details of 13 children with clinical diagnosis of hyperinsulinemic hypoglycemia were reviewed, retrospectively. The scans were acquired 30–45 min postinjection of 2–3 mCi of 18F-DOPA on dedicated PET/CT scanners (BiographmCT, Siemens Inc. and Discovery PET/CT, GE). Abdominal spots over 1–2 bed positions were acquired. In addition, genetic mutation status of ABCC8 and CGK1 was analyzed with respect to the scan findings. Results: Of the 13 patients (seven female and six male), nine were infants. The age of the patients ranged from 3 months to 7 years. Seven patients had undergone mutation analysis of which six were ABCC8 positive and one was CGK1 positive. Six patients (46%) were positive for focal lesions on 18F-DOPA PET/CT scan, while 6 (46%) were negative for focal lesions. One was indeterminate on 18F-DOPA scan. Of the six ABCC8 mutation-positive patients, 4 (67%) were positive on DOPA scan while two were negative for focal lesion. However, of the six patients with unknown mutation status, only 1 (17%) was positive on DOPA scan, and 1 (17%) was indeterminate. Conclusion: 18F-DOPA PET/CT is a useful modality for localizing culprit pancreatic lesions in children with persistent hyperinsulinemic hypoglycemia. The detection rate is significantly higher in patients with ABCC8 gene mutation. It is therefore recommended to ascertain the genetic mutation status of such patients before conducting the 18F-DOPA PET/CT study.
| PP2: Molecular imaging to the surgeon's rescue: 68Gallium-DOTA-exendin-4 positron emission tomography/computed tomography in preoperative localization of insulinomas | | |
U. N. Pallavi, Ishita B. Sen, Vindhya Malasani, Parul Thakral, Vineet Pant, D. Sugandha
Fortis Memorial Research Institute, Gurugram, Haryana, India
Background and Objectives: Insulinoma is an islet-cell adenoma that secretes insulin. It is usually localized to the pancreas and is often the most common cause of endogenous hyperinsulinemic hypoglycemia in nondiabetic adult patients. Surgical excision with curative intent is the standard modality of treatment, and it requires precise localization of tumor tissue. 68gallium-DOTA-exendin-4 positron emission tomography/computed tomography (PET/CT) scan is a clinically reasonable and sensitive scan for the identification of insulinoma. The aim of this retrospective study was to determine the overall accuracy of 68gallium-DOTA-exendin-4 PET/CT scan in the detection of insulinoma. Materials and Methods: Eight patients with fasting hyperinsulinemic hypoglycemia with neuroglycopenic symptoms were enrolled in this study. Whole-body PET/CT scan was performed on a Philips Time-Of-Flight PET/CT scanner, 60 min after injection of 68gallium-DOTA-exendin-4. The imaging findings were compared to the histopathological diagnosis in six out of eight patients and to subsequent follow-up in the remaining two patients who did not undergo surgery. Results: The sensitivity and specificity of 68gallium-DOTA-exendin-4 PET/CT scan in insulinoma detection were found to be 75% and 100%, respectively. Overall accuracy was 87.5%. Conclusion: 68Gallium-DOTA-exendin-4 PET/CT scan is highly sensitive for identification and exact localization of insulinoma which can guide better surgical exploration. However, randomized controlled trials are needed to assess the accuracy of 68gallium-DOTA-exendin PET/CT scan in localization of insulinoma.
| PV4: False-negative Tc-99m sestamibi parathyroid scan: A case series | | |
Anbalagan Kannivelu
Khoo Teck Puat Hospital, Singapore
Background and Objectives: Retrospectively, we collected the T-99m sestamibi parathyroid scans performed in our institution for the last 1 year and selected the cases who underwent surgery. Among those patients (n = 36), we selected the scans which were false negative (n = 5). We analyzed those cases and tried to identify the most possible reason for poor sensitivity. We present them as a case series. Case 1: A 73-year-old female patient had two parathyroid lesions, a bigger lesion on the right and a smaller lesion on the left. Left-sided lesion is not seen in the scintigram. Surgical exploration and histopathological examination confirmed adenoma of both parathyroid glands. The study is likely false negative due to the left-sided lesion's small size. Case 2: Similar to Case 1, a 60-year-old female patient had two parathyroid lesions, a bigger lesion on the right and a smaller lesion on the left. Left-sided lesion is not picked up in the scintigram, most likely due to its small size. Case 3: A 60-year-old male patient had a 1.5-cm parathyroid lesion on the left side seen on ultrasound. The scintigram is negative; however, the surgical exploration and histopathological examination confirmed the presence of parathyroid adenoma. Reason for false negativity in this study could not be ascertained. Case 4: A 70-year-old female patient had a suspicious left parathyroid lesion on ultrasound, and scintigram was negative. Surgical exploration revealed enlarged left superior parathyroid gland and prominent other three glands. These glands showed hyperplasia on histological evaluation and none of them was adenoma, and this was considered as the possible cause for false negativity. Case 5: Ultrasonography revealed a large nodule suggestive of a right parathyroid adenoma in a 62-year-old female patient with background features of thyroiditis. The patient was clinically hyperthyroid but normocalcemic. Scintigram was negative for parathyroid adenoma and thyroid gland showed intense and persistent uptake up to 5 h postinjection. False negativity in this case was attributed to the normocalcemic status. Conclusion: Parathyroid scintigraphy is useful for confirmation and presurgical localization of parathyroid adenoma(s) in hyperparathyroidism patients. As reporting nuclear medicine physicians, we should be aware of the fact that about 5%–15% of scans are false negative, especially in smaller lesions, normocalcemic patients and parathyroid hyperplasia. In our small group of patients, the calculated false-negative rate is 14%.
| Liver/GB/GI Track | | |
| OP6: Response to transarterial Re-188 HDD lipiodol therapy in hepatocellular carcinoma with malignant portal vein thrombosis | | |
Shreya Datta Gupta, Shamim A. Shamim, Priyanka Gupta, G Shivanand1, Shalimar2, Priyanka Singh, Chandra Sekhar Bal
Departments of Nuclear Medicine, 1Radiodiagnosis and 2Gastroenterology, AIIMS, New Delhi, India
Background and Objectives: Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related deaths. HCC with malignant portal vein thrombosis (PVT) has grave prognosis due to limited treatment options. Transarterial chemoembolization (TACE) is commonly used when disease is limited to the liver. However, in case of extensive portal vein involvement, TACE is generally contraindicated. Transarterial radionuclide therapy, on the other hand, can still be performed. Our aim was to assess the role of Re-188 HDD lipiodol therapy in HCC with malignant PVT. Materials and Methods: Patients with locally advanced HCC having PVT were recruited from the liver cancer clinic. Baseline triple-phase magnetic resonance imaging (MRI) liver and serum alpha-fetoprotein (AFP) levels were recorded. Empirical dose of Re188-HDD lipiodol was estimated and prepared under aseptic conditions. Transarterial access was gained under fluoroscopy in the Department of Radiodiagnosis. Patients before administration of full dose underwent a scout dose scan (~185 MBq Re-188 HDD lipiodol) to look for hepatopulmonary shunts. Therapeutic dose was then injected into the tumor-feeding vessels. Patients remained hospitalized for a minimum period of 72 h. Planar and single-photon emission computed tomography-computed tomography scans were acquired at 6, 24, and 48 h. Clinical, radiological, and biochemical follow-up was done at 3 and 6 months posttherapy. Results: Six patients (five males, one female) of HCC with malignant PVT were recruited. Patients' mean age was 61.3 years (±4.2). All recruited patients were Eastern Cooperative Oncology Group (ECOG) performance status 2 or less. Mean dose injected was 2.74 ± 0.11 GBq of Re188-HDD-lipiodol. No serious adverse events were noted in any patient during the hospital stay. However, one patient deteriorated in the 2nd week and died due to hepatic encephalopathy. On follow-up, two of the remaining five patients showed complete biochemical and radiological response (mRECIST) by 3 months. Fall in AFP noted in these two were from 647 to 28.5 and 22,000 to 184 ng/ml. Two patients showed biochemical and radiological stable disease at the end of 2 months; one of who died after developing peritoneal infection 4 months after therapy. One patient showed radiological stable disease, but biochemical progression and further investigations revealed pulmonary metastasis. Minimum follow-up was 5 months, and four of the six patients are alive, with improvement of ECOG status and no further clinical progression in three. Conclusion: Re-188 HDD lipiodol therapy can be a useful option in patients of HCC with malignant PVT, showing an improvement in quality of life.
| OP7: Liver function assessment by quantitative 99mTc sulfur colloid liver single-photon emission computed tomography in decompensated cirrhosis following granulocyte colony-stimulating factor therapy | | |
Amritjyot Kaur, Baljinder Singh, Virendra Singh1, Anish Bsshattacharya, Nipun Verma1, Arka De1, Shalini Chopra
Department of Nuclear Medicine and 1Hepatology, PGIMER, Chandigarh, India
Background and Objectives: Decompensated cirrhosis (DC) portends high morbidity and mortality worldwide. Liver transplant is the definitive treatment, but it is limited due to high expenses, lifelong use of immunosuppressants, and side effects. Granulocyte colony-stimulating factor (GCSF) therapy for liver cirrhosis, an affordable and effective treatment, has shown encouraging results. To predict the outcome of this therapy, an accurate quantitative determination of liver function is critical. In the present study, we have evaluated the role of 99mTc-sulfur colloid liver single-photon emission computed tomography (SPECT) for quantifying liver function in patients with DC after multiple courses of GCSF. Materials and Methods: A total number of 66 patients (57 males, 9 females; mean age 55.8 ± 10.4 years) with DC were enrolled and prospectively randomized in an open study with two groups: A and B. Group A (n = 38) received standard medical therapy (SMT) with four cycles of GCSF (at a dose of 5 μg/kg subcutaneously every 12 h for 5 days [first cycle], every 3rd month for 3 days [remaining cycles] for 1 year). Group B (n = 27) received only SMT. Follow-up was done every month for 1 year. Disease severity: Child-Pugh Score (CTPs) and model for end-stage liver disease (MELD) scores were recorded every month for patient assessment. 99mTc sulfur colloid SPECT/CT was performed at baseline, 6th month, and 12th month in both the groups. Quantitative liver uptake (QLU) and percentage injected dose/ml in liver tissue were calculated and statistically analyzed. Results: Baseline characteristics were comparable between the groups. In Group A, baseline and 12th month QLU was found to be 26.68 ± 15.50 and 28.76 ± 13.99, respectively (P = 0.387). However, in Group B, QLU decreased from 28.23 ± 8.20 at baseline to 17.78 ± 10.86 at 12th month (P = 0.002). Survival rates at 12th month for Groups A and B patients were 71.8% and 56.5%, respectively (P = 0.017). Over 12 months, median CTP improved in Group A (9.5 [7–11] to 7 [5–9]; P = 0.01) but remained same in Group B (9 [6–12] to 9 [5–13]; P = 0.052). Median MELD scores also improved in Group A (14.5 [9–21] to 10 [8–16]; P = 0.001) and Group B (14 [9–20] to 18.5 [10–24]; P = 0.05). Conclusion: Multiple courses of GCSF showed comparable values of QLU in baseline and 12th month. However, group without GCSF course showed significant decrease in QLU at 12th month from baseline. These results are in concordance with disease severity CTP and MELD scores. The study has shown 99mTc-sulfur colloid liver SPECT as a useful, noninvasive quantitative test for assessment of liver function.
| PP3: Impact of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography on preoperative patients of carcinoma gallbladder | | |
Ashutosh Parashar, Manish Ora, M. M. Singh, Kasturi Rangan
Department of Nuclear Medicine, SGPGI, Lucknow, Uttar Pradesh, India
Background and Objectives: Incidental diagnosis of gallbladder cancer is becoming the major concern in northern populace of India. The role of positron emission tomography-computed tomography (PET-CT) in modifying the extent of surgery and adjuvant treatment is still largely unexplored. Hence, we retrospectively evaluated the impact of 18F-labeled fluoro-2-deoxyglucose [18 F] FDG PET-CT made at preoperative scenario. Materials and Methods: This is a retrospective analysis of suspected gallbladder cancer patients who underwent PET-CT for staging and pretherapy evaluation. Results: A total of 78 preoperative patients were analyzed, with female-to-male ratio of 64:36. In these cases, average SUVmax of primary lesion was 8.19 (maximum 25.9), with local infiltration noted in 48 patients (SUVmax 6.65). Liver metastasis was found in 34 patients of which 29 had oligometastasis (SUVmax 8.5) and multiple liver metastases noted in five patients (SUVmax 7.9). Lymph nodal spread was noted locally in 37 patients (SUVmax 6.5) and distant in 13 patients (average SUVmax 4.9). Omental involvement was noted in two patients (SUVmax 14.10). Involvement of bone was noted in 10 patients (SUVmax 6.6) and other organ involvement in 30 patients (SUVmax 5.6). Conclusion: PET-CT scan makes an enormous impact in stratifying patients with incidentally diagnosed gallbladder cancer. Liver wedge resection may be avoided in all infiltration negative patients. Apart from surgery, patients with liver metastasis and distant metastasis can be taken up for chemotherapy.
| PP4: Comparison of fluoro-2-deoxyglucose positron emission tomography-computed tomography and contrast-enhanced computed tomography in the evaluation of postoperative colorectal carcinoma patients with elevated serum carcinoembryonic antigen levels | | |
M. V. Manikandam, Archi Agrawal, Nilendu Purandare, Sneha Shah, Ameya Puranik, Venkatesh Rangarajan
Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India
Background and Objectives: As per the NCCN guidelines, the suggested options for evaluation of postoperative colorectal carcinoma patients with rising serum carcinoembryonic antigen (CEA) levels are either a combination of contrast-enhanced computed tomography (CECT) neck, chest, and abdomen-pelvis or fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT). In our institution, PET/CT is being done as the standard of care. This gave us the impetus to compare the two imaging modalities to see if one is superior over the other. In this retrospective analysis, our aim was to compare the role of FDG PET/CT and CECT in the detection of recurrence in colorectal carcinoma patients with elevated serum CEA levels. Methodology and Results: Scans of 79 patients in the age group of 28–86 years were analyzed. Serum CEA ranged from 2.8 to 3398 ng/ml. The findings of PET-CT and CT were concordant in 74 patients – 93.6%. Among these 74 patients with concordant results, both CECT and PET/CT were normal in 15 patients, i.e., 18% of total patient population. Discordant results were seen in five patients (6.4%). Conclusion: In our analysis, we could not find any significant incremental value of FDG PET/CT over CECT scan in the detection of recurrence in patients with elevated serum CEA levels. However, in patients with serum CEA level less than 10 ng/ml, detection of tiny liver lesions, nodes, and marrow disease by CECT is still a challenge, where PET/CT could be beneficial. In patients with CEA values >10 ng/ml, either of the two modalities could be chosen depending upon the institutional policy. This study needs to cary out with more number of patients to evaluate the efficiency of FDG PET/CT in these situations.
| PV5: Impact of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography on postoperative patients of carcinoma gallbladder | | |
Ashutosh Parashar, S. Gambhir, Man Mohan, Manish Ora, Aftab, P. K. Pradhan
Department of Nuclear medicine, SGPGI, Lucknow, Uttar Pradesh, India
Background and Objectives: Incidental diagnosis of gallbladder cancer is becoming the major concern in northern populace of India. The role of positron emission tomography-computed tomography (PET-CT) in modifying the extent of surgery and adjuvant treatment is still largely unexplored. Hence, we retrospectively evaluated the impact of 18F-labeled fluoro-2-deoxyglucose ([18 F] FDG) PET-CT made at postoperative scenario. Materials and Methods: This is a retrospective analysis of patients who were operated for gallbladder cancer and underwent PET-CT for restaging and posttherapy evaluation. Results: A total of 61 postoperative patients were analyzed, with female-to-male ratio of 60:40. In these cases, 40 patients were found to have extensive metastasis, of which liver lesions were noted in 21 patients (oligo – 15, multiple – 7, with SUVmax – 9.7), metastatic local lymph node in 24 patients (SUVmax – 3.9), and abdominal lymph nodes in 14 patients (SUVmax – 4.8), bony metastasis in three patients (maximum SUVmax – 5), and skin seeding were noted in nine patients (maximum SUVmax – 12.8). In addition to all these lesions, omental deposits were noted in nine patients with maximum SUVmax of 5.4. Conclusion: PET-CT scan makes an enormous impact in stratifying patients with gallbladder cancer. Liver wedge resection may be avoided in all infiltration negative patients. Apart from surgery, patients with liver metastasis and distant metastasis can be taken up for chemotherapy.
| PV6: Feasibility of intra-arterial Lu-177 DOTATATE therapy in metastatic neuroendocrine tumors with liver dominant disease: “A novel theranostic approach to augment therapeutic potential” | | |
Arvind Rajan, S. Sumati, Deepa Shree1
Department of Nuclear Medicine and Therapy and 1Interventional Radiology, Gleneagles Global Hospitals, Chennai, Tamil Nadu, India
Background and Objectives: A few recent preclinical and clinical studies have demonstrated a higher first pass effect with a higher tumoral uptake during intra-arterial Ga-68 DOTANOC imaging of liver metastasis in neuroendocrine tumors (NETs). It has been hypothesized that this novel approach could be translated into theranostics. The aim of this study was to assess the safety, tolerability, and efficacy of intra-arterial Lu-177 DOTATATE therapy in patients within patients with liver-dominant metastasis in well-differentiated NET. Materials and Methods: Four patients with well-differentiated liver-dominant neuroendocrine metastasis were given four cycles of 200 mCi of Lu-177 DOTATATE therapy intra-arterially, at intervals of 8 weeks. Their complete blood counts, liver function, renal function, and coagulation profiles were assessed within 2 weeks before each treatment cycle, in the immediate posttherapy period, and within 6 weeks posttreatment. Radiological assessment and tumor markers were also assessed pre- and post-treatment. Results: Significant reduction in serum chromogranin A levels with partial reduction in size and tracer uptake in all patients was noted. None of the patients experienced any acute side effects or unexpected complication during therapy or in the immediate posttherapy period, except for nausea, vomiting, and mild right-sided abdominal pain which was managed conservatively. No acute radiation-induced lung disease or renal toxicity seen in any patient after 2 months of follow-up. Liver functions remained stable with improved quality of life. All four patients developed Grade-I hematotoxicity with prolonged recovery, two patients developed mild (<2 times) increase in serum alkaline phosphatase (ALP) and serum gamma-glutamyltransferase (GGT) levels persisting for a month after therapy. One patient developed moderate increase (>2.5 times) in serum ALP and serum GGT levels with mild reduction in total protein. No significant reductions in serum total bilirubin levels were seen in any of the patients. Conclusion: The initial experience of intraarterial administration of Lu-177 DOTATATE therapy in patients with liver-dominant metastasis is promising as a safe and tolerable treatment. However, treatment efficacy and survival benefits will be evaluated after 1 year of follow-up with larger number of patients.
| Musculoskeletal Track | | |
| OP8: [18F] fluoride positron emission tomography/computed tomography bone scan in diagnosis of avascular necrosis of femoral head and follow-up after core decompression surgery | | |
Shankaramurthy Gayana, Anish Bhattacharya1, Ramesh Kumar Sen2, Paramjeet Singh3, Mahesh Prakash3, Bhagwant Rai Mittal1
New Medd Diagnostics, Bengaluru, Karnataka, Departments of 1Nuclear Medicine, 2Orthopedics and 3Radiodiagnosis, PGIMER, Chandigarh, India
Background and Objectives: The purpose of this study was to compare [18F] fluoride positron emission tomography/computed tomography (PET/CT) bone scan with magnetic resonance imaging (MRI) in the initial diagnosis of avascular necrosis of the femoral head (FHAVN) and after core decompression (CD) surgery to evaluate the healing process. Materials and Methods: We studied 51 patients with a high clinical suspicion of FHAVN. Forty of these patients were finally diagnosed as having FHAVN on both MRI and [18F] fluoride PET/CT bone scan and 16/40 were reevaluated with clinical assessment using the Harris hip score (HHS), MRI, and [18F] fluoride PET/CT bone scan 6 months after surgery. Results: Five of the 16 (31%) patients included in the final analysis had unilateral and 11 (69%) bilateral FHAVN; a total of 27 hips were analyzed. FHAVN was diagnosed by a photopenic area surrounded by increased radiotracer uptake on PET, with “crescent” and “asterisk” signs on CT. Of the 27 hips diagnosed with FHAVN on MRI, 10 were diagnosed to be Association for Research on Osseous Circulation (ARCO) Stage II and 17 as ARCO Stage III at initial presentation. There was no significant difference in the affected femoral heads between the baseline and postsurgery MRI scans. However, follow-up PET/CT showed improved [18F] fluoride concentration corresponding to the photopenic area on the baseline scans, suggestive of ongoing revascularization. The mean SUVmax of the affected femoral heads was 24.0 (7.4) before surgery and 19.0 (6.3) in the post-CD scan. The paired sample t-test showed a statistically significant difference (P = 0.000) between these values. The mean SUVmax of the photopenic area of the affected femoral heads at baseline was 1.8 (0.6) while that of the corresponding area of relatively reduced tracer uptake at 6 months after CD was 2.9 (1.3). This difference was statistically significant (P = 0.000). The difference between mean HHS at baseline (81.3 [11.6]) and after surgery (84.2 [12.2]) was also statistically significant (P = 0.024). There was significant correlation between SUVmax on PET and HHS. Conclusion: [18F] fluoride PET/CT bone scan shows good agreement with MRI in the initial diagnosis of FHAVN and demonstrates improvement in femoral head viability earlier than MRI in post-CD patients.
| OP9: Incremental value of 99mTc MDP single photon-emission computed tomography-computed tomography over planar scintigraphy in different skeletal pathologies | | |
Shamim Ahmed Shamim, Averilicia Passah, Saurabh Arora, Anirban Mukherjee1, Girish Kumar Parida, Ravi Kant Gupta, Sarthak Tripathy, Chandra Sekhar Bal, Shreya Datta Gupta
Department of Nuclear Medicine, AIIMS, 1Eastern Diagnostics India Ltd., New Delhi, India
Background and Objective: To assess the incremental value of single photon-emission computed tomography-computed tomography (SPECT-CT) over planar scintigraphy in different skeletal pathologies. Materials and Methods: A total of 66 patients were recruited prospectively, having different skeletal pathologies including osteomyelitis (42), prosthesis loosening (6), avascular necrosis (4), myositis ossificans (2), osteoid osteoma (1), graft viability (1), condylar hyperplasia (1), metastasis (1), and others (8). Follow-up was available for 60 patients. All patients underwent planar bone scan initially. Additional SPECT-CT imaging was acquired in 40 patients having equivocal finding on planner scintigraphy. Histopathology/microbiology/clinical imaging/follow-up was used as the reference standard. Results: The average age of the patients was 36.56 years and range is 10–76 years. There were 39 male patients and 21 female patients. Of the 60 patients, the diagnosis was conclusive on planar scintigraphy in 20 patients and 40 patients diagnosis was equivocal on planar scintigraphy. These 40 patients underwent additional SPECT-CT. SPECT-CT was true positive (TP) in 33 patients, true negative (TN) in one patient, false positive in five patients, and false negative in one patient. The accuracy (TP + TN) of SPECT-CT was found to be 85%. SPECT-CT showed an incremental value of about 56% over planar scintigraphy in different skeletal pathologies. Conclusion: SPECT-CT showed an incremental value of about 56% over planar scintigraphy in characterization of different skeletal pathologies.
| OP10: Impact of three-phase bone scintigraphy in active management of rheumatoid arthritis | | |
Vivek Kumar Saini, Sanjay Gambhir, Amitabh Arya, Manish Ora, A. H. Nazar, Ashutosh Prashar, Akshay
Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
Background and Objectives: The aim of this study was to evaluate the utility of three phase bone scan in rheumatoid arthritis (RA) and its biochemical correlation. Materials and Methods: It is a prospective study in which 30 patients of RA were included. All patients diagnosed according to the ACR/EULAR 2010 criteria of RA. Rheumatoid factor (RF), anti-cyclic citrullinated antibody (anti-CCP antibody) and erythrocyte sedimentation rate (ESR) were evaluated. According their biochemical findings, the patients were divided in the two groups. Fifteen patients had RF or anti-CCP antibody <30 RU/ml and <30 IU/ml, respectively. Second group had RF or anti-CCP antibody >30 RU/ml and >30 IU/ml, respectively. Total number of joints involvement was evaluated (large and small) and correlated according to biochemical findings. Results: A positive correlation was noted in biochemical finding and total number of joint involvement. First group had a total of 180 joint involvements (75 large joint and 105 small joint) and second group had a total of 210 joint involvements (100 large and 110 small joints). Conclusion: This study shows a good correlation in the three phase bone scintigraphy and biochemical findings, indicating that three phase bone scintigraphy can be used as a good tool in the active management of patients with RA.
| OP11: Postsurgical evaluation of bone viability in autogenic vascularized bone graft with or without flap by18F-NaF-positron emission tomography/computed tomography | | |
Arpana Arbind, Shwetal Pawar, Bhairavi Bhatt, Amresh Baliarsing1, Vineet Kumar1, Kumar Krishna1, Shakti Zeriel
Department of Nuclear Medicine and PET Imaging, Seth S. G. Medical college and KEM Hospital, 1Department of Plastic Surgery, Topiwala National Medical College and B. Y. L. Nair Charitable Hospital, Mumbai, Maharashtra, India
Background and Objectives: Vascularized bone grafting is a versatile technique for reconstructing large bone defects. After the bone grafting, early perioperative monitoring is critical to detect the postoperative complications. After a bone graft, there is a lack of direct access to the grafted segments, which makes the postoperative monitoring particularly challenging. The most commonly used method for the assessment of bone graft viability is bone scintigraphy, which is routinely done by technetium-99m MDP. Due to many superior qualities 18F-NaF positron emission tomography/computed tomography (PET/CT) is replacing 99mTc-MDP scan in many clinical applications (both oncological and nononcological). In this study, an early dynamic 18F-NaF-PET/CT scan was performed in addition to the delayed standard PET/CT scan in all patients. The study aims to evaluate the role of 18F-NaF PET/CT in bone viability in autogenic vascularized bone graft with or without flap and correlate the 18F-NaF uptake qualitatively and quantitatively with clinical outcomes. Materials and Methods: 18F-NaF (mean dose 185 MBq) was injected; early dynamic (5-min imaging) and then delayed (60 min postinjection) PET/CT (regional) scan were done. Manually, region of interest was drawn over grafted segments and contralateral reference bone. Time–activity curves (TACs) were generated on perfusion image and graded qualitatively. Grade 0 (no uptake) and 1 (less than reference bone) considered as ischemic and Grade 2 and 3 (equal to and more than reference bone respectively) considered as good perfusion. Delayed images SUVmax ratios were calculated between grafted bone segments and contralateral reference bone. Grafted segments which showed qualitative grade 2 or 3 on perfusion and SUVmax ratio of 1 were considered as viable. Grafted segments which showed qualitative grade of 0 or 1 on perfusion and the SUVmax ratio of 1 is considered as non-viable. Results: In this study, a total of 19 patients (8 females, 11 males) with bone graft were included. 29/35 (83%) grafted segments were noted as viable. 6/35 (17%) segments were nonviable. The average SUVmax ratio of grafted and reference bone was 3.35 in the viable group and 0.82 in the nonviable group. The SUVmax values in the grafted viable segment were significantly high in comparison to reference bone (P = 0.00013). On following these patients, 14/19 (73 %) patients viable bone grafts had no complaints, 2/19 (10 %) had features of infection, and 3/19 (16%, corresponding to 6 grafted segments) were nonviable and were reexplored. Conclusion: 18F-NaF-PET/CT is correctly differentiated between viable and nonviable grafted segments on basis of perfusion and SUVmax ratios in early dynamic and delayed images.
| PP5: Role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in documenting the disease burden in brain tuberculosis and Potts spine | | |
Kasturi Rangan, Sanjay Gambhir, Mudalsha Ravina, Nikhil Kakani1, Ajay S. Suraj
Department of Nuclear Medicine, SGPGIMS, 1Department of Neurosurgery, KGMC, Lucknow, Uttar Pradesh, India
Background and Objectives: The study aims at demonstrating the potential use of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (F18 FDG-PET/CT) in documenting the findings in brain and spinal tuberculosis and to compare its finding with site-specific magnetic resonance imaging (MRI), and finally, to evaluate its impact in documenting the disease burden in baseline, to monitor the disease status in follow-up of the patients, and to establish a therapeutic end point. Materials and Methods: A total of 63 patients were recruited (male:female – 1.4:1, median age – 46 years), of which 40 were diagnosed with spinal tuberculosis and 23 were that of brain tuberculosis with the help of MRI or pathologically. Standard [18F] FDG-PET/CT imaging was done at baseline and its results with compared with site specific MRI. On follow-up after starting anti-tubercular treatment (HRZE), only [18F] FDG-PET/CT was done at 2 and 6 months and the results were compared with baseline scan. Based on the metabolic response in the follow-up scans, subjects were categorized as progressive disease (PD), stable disease (SD), partial response (PR), or complete metabolic response (CMR). Results: Baseline 18F-FDG PET/CT results were compared with regional-specific MRI, which revealed good agreement between the two modalities (Kappa – 0.809) for delineating tuberculoma (average SUVmax 5.8, number 23), basal exudates (SUVmax 10.23), chronic infarcts (4 patients), vertebral involvement (40 patients, average SUVmax 14.2), paravertebral soft tissue (SUVmax 12.14) and also revealed additional findings such as diffuse spinal uptake (4 patients, average SUVmax 4.7), lymph nodal involvement (18 patients, cervical and mediastinal group), lung lesions (16 patients), psoas abscess (5 patients), and some special cases such as aortic arch aneurysm and osteomyelitis. In follow-up study, 30 subjects underwent second scan, among which seven had CMR, 20 had PR, and three with PD. Third follow-up was done in eight out of 24 subjects, among which four had CMR, two had PR, and two with PD. Progressive disease patients were confirmed to have multidrug-resistant disease status. Conclusion: Whole-body 18-F-FDG-PET/CT has a splendid role in delineation of actual disease burden in tuberculosis which is not possible with regional specific imaging. Significant number of patients have partial response to treatment in 6 months, indicating need for completing the extended regimen of treatment to achieve complete response. Thus, it can be a one shop stop modality in assessing the disease burden at the start of the treatment, can play a pivitol role in individualizing management, can monitor disease status, and can help in guiding the physicians to reach the therapeutic end point.
Acknowledgment: We would like to acknowledge IAEA, Coordinated Research Project E 15021.
| PP6: A comparison between 99mTc ubiquicidin and 99mTc-methylenediphosphonicacid bone scan for prosthetic loosening evaluation | | |
R. Venkatesh, Ajit Shinto1, A. Mukherjee2, E. R. Radhakrishnan1, S. Arun Pandian1, A. Dash2, F. R. Kingsley1, Raghi P. Jose1, V. J. Arnold1, K. K. Kamaleswaran1, B. Surya1
Kovai Medical Centre Research and Educational Trust, 1Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, 2Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: The prosthetic evaluation was developed specifically to provide functional outcome measures in prosthetics that are more turned to prosthesis-related changes in quality of life. Uptake of 99mTc MDP in a bone scan depends on two factors via the vascularity and the local osteogenesis. Thus, there are two distinct pathophysiologies for the positivity bone scan; one related to the delivery of the radiotracer to the site of the lesion and other with the incorporation of the radiotracer with the hydroxyapatite crystal of the bone. 99mTc-ubiquicidin is a synthetic cationic antimicrobial peptide that preferentially binds to bacterial cell membrane at the site of infection. The study aims to compare 99mTc-ubiquicidin and 99mTc-methylenediphosphonic acid bone scan for prosthetic loosening evaluation. Materials and Methods: Thirty patients with suspected prosthetic evaluation of hip joint and knee joint were selected for this study. First a routine three phase bone scan was done with 99mTc –MDP. Blood flow, blood pool and delayed images of SPECT were done respectively, followed by 99mTc ubiquicidin. Scan was performed after intravenous injection of 15 – 20 mCi of 99mTc ubiquicidin. A 10-min dynamic study was followed by spot views of the suspected region of infection and corresponding normal areas (liver, kidney) at 60 and 120 min. Whole-body anterior and posterior images were also acquired. We compared the two scan of 99mTc-MDP three phase bone scan and 99mTc-ubiquicidin for prosthetic evaluation of hip joint and knee joint. Comparison was done on the basis of the increased tracer uptake in blood pool imaging. If the three phase bone scan has increased uptake and 99mTc-ubiquicidin scan also has increased uptake, then this scan is considered positive for septic infection. In comparison, if the three phase blood pool scan has increased uptake and the ubiquicidin scan has no uptake, then this scan is considered negative suggests aseptic infection. Results: The combination of 99mTc-MDP and ubiquicidin scans correctly identified infective loosening in 15 of 16 patients (true positive). Aseptic loosening scans finding were noted in 9 of 14 patients. Hence, the PPV, NPV, sensitivity, and specificity were 75%, 90%, 93.75%, and 64.2%, respectively. Conclusion: The 99mTc-ubiquicidin is a processing tool for diagnostic of septic loosening in prosthetic patients.
| PV7: Role of fluoro-2-deoxyglucose positron emission tomography-computed tomography in staging and follow-up of patients with synovial sarcoma | | |
Shamim Ahmed Shamim, Shreya Datta Gupta, Averilicia Passah, Rakesh Kumar, Chandra Sekhar Bal, Madhavi Tripathi
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objective: Synovial sarcoma is a rare malignancy, comprising only 6%–10% of all soft tissue sarcomas. It affects the lower limbs more often and diagnosis is usually delayed due to gradual onset. Nearly 50% of the synovial sarcomas tend to recur locally within 2 years and 50%–70% metastasize up to 5 years later, requiring long follow-ups. Our aim in this study was to assess the role of fluoro-2-deoxyglucose positron emission tomography-computed tomography (FDG PET-CT) in the baseline staging and follow-ups in cases of synovial sarcoma. Materials and Methods: Cases of synovial sarcoma undergoing FDG PET-CT in the Department of Nuclear Medicine in our institute in the last 2 years for baseline staging and follow-ups postinterventions were included in the study. An expert nuclear physician reported FDG PET-CT scans of the patients. Patients with multiple scans were evaluated for response using the PERCIST criteria. Results: A total of eight patients, five males and three females, were included. The mean age of the patients was 27.4 years (±8.7) and four out of eight had primary tumors in the lower limb. Two of the eight patients came for baseline disease status evaluation, one of who was found to have additional lung metastases. Two other patients presented postsurgical resection for disease status and both of them were detected to have residual disease. One of them was also diagnosed with lung nodules and the other with nodal metastases. One patient underwent FDG PET-CT postdebridement followed by local radiotherapy; this patient was also detected with pulmonary and nodal metastases on PET-CT. Two patients with known pulmonary metastases were followed up over three interval scans. One patient initially showed complete response after chemoradiation and later relapsed within a year again. The second patient was noted to have a stable disease on PET-CT. One patient with no baseline scan presented with the suspicion of recurrence, which was confirmed on FDG PET-CT. Overall, four out of eight (50%) patients were upstaged after FDG PET-CT and one detected with recurrence. Conclusion: FDG PET-CT has a role in staging of synovial sarcoma as well as in screening for recurrences. Since it is known to recur and metastasize years later, FDG PET-CT can be considered as an important tool in the follow-up of these patients for early detection and management. More studies would be required to assess its role in response to treatment.
| PV8: Evaluation of correlation between triple phase bone scintigraphy and single-photon emission computed tomography/computed tomography in diagnosis of traumatic complex regional pain syndrome | | |
Avinash Tupalli, Nishikant Avinash Damle
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: Although the diagnosis of complex regional pain syndrome (CRPS) is predominantly clinical, it is often supported by supplemental examinations such as three phase bone scans (TPBS). However, the role of single-photon emission computed tomography (SPECT)/CT has not been evaluated in these cases. The objective of this study was to assess the correlation between TPBS and SPECT/CT in patients with suspected traumatic CRPS. Materials and Methods: A retrospective review of TPBS and SPECT/CT done in 73 patients with clinically suspected CRPS between January 2017 and April 2018 was done. TPBS consisting of a dynamic flow study, blood pool, and delayed static whole-body and regional static imaging 3 h postinjection of 10–20 mCi (370–740 MBq) 99mTc-MDP and SPECT/CT was done. Planar scans were reported as positive or negative for CRPS based on the institutional protocol supported by Budapest criteria. SPECT/CT of these patients were interpreted separately for additional findings including increased periarticular uptake, focal increase in tracer uptake at traumatic site, and atrophic changes of affected region. Results: Out of 73 patients, 34 were male and 39 were female (age: 12–79 years). Of 73, 46 (63%) of these provisionally diagnosed cases were scintigraphically positive for CRPS, while 27 were reported negative. Correlation coefficient of TPBS and clinical diagnosis was 0.876 (strong positive) while that for SPECT/CT was 0.739 (moderate positive). Thirteen positive scans on planar bone scan were reported to be negative on SPECT/CT due to focal increased uptake at fracture site and lack of CT features of CRPS. TPBS and SPECT/CT were concordant in 60/73 (82%) patients (Kappa = 0.576; P < 0.05). Conclusion: Our results showed that there is high concordance between clinical diagnosis and TPBS findings and moderate concordance between clinical diagnosis and SPECT/CT findings. In the absence of definitive SPECT/CT criteria in the diagnosis of CRPS, it is unclear whether SPECT/CT indeed reduces false positives and can be assessed by prospective cohort study.
| PV9: Evaluation of planar image findings with regional single-photon emission computed tomography/computed tomography in bone imaging for metastatic workup | | |
Manishi L. Narayan, Ashok Kumar, Sanchay Jain, Vandana K. Dhingra
Department of Nuclear Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
Background and Objectives: Bone scintigraphy continues to be the most cost-effective and reliable method for screening skeletal metastasis. Method of imaging includes whole-body planar imaging routinely, additional views, and/or single-photon emission computed tomography (SPECT) or SPECT/CT is done to increase diagnostic accuracy of the bone scan. However, because of additional time needed and added radiation burden with CT, SPECT/CT is not usually performed in all cases. The aim of this study was to analyze the additional diagnostic value of SPECT/CT imaging compared with SPECT and planar imaging in patients referred for bone scan for metastatic workup. Materials and Methods: We retrospectively analyzed 99mTc-MDP bone scans of 31 patients (22 males and 9 females) who were referred for metastatic workup, where SPECT/CT was performed in addition to planar images. SPECT/CT images were compared with SPECT and planar image findings. Results and Conclusion: Five out of 31 (16.1%) patients showed additional lesion(s) on SPECT/CT (osteolytic, mixed, and osteoblastic). Three out of these patients did not show any abnormality on planar or SPECT only images (renal cell carcinoma, carcinoma tongue); however one of these five patients showed photopenic lesion on SPECT image while planar was negative and one patient showed equivocal finding on SPECT/CT (carcinoma cervix), which turned out to be an osteolytic lesion on corresponding CT images [Table 1]. In the current study, there was an additional diagnostic yield of 16.1% for detection of metastatic lesion with SPECT/CT. When planar images are negative, SPECT/CT imaging is more useful in malignancies with high probability of lytic metastasis.
| PV10: Extraosseous diffuse intense muscular uptake on 99mTc-MDP bone scan and 18F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography in a case of inflammatory myopathy | | |
J. Sai Moulika, R. Ramya Priya, V. S. Krishna Mohan, Ranadheer Manthri, T. C. Kalawat
Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
Introduction: Inflammatory myopathies are a group of disorders that include polymyositis (PM), dermatomyositis, autoimmune necrotizing myopathy, and inclusion body myositis. They have a female preponderance, with unknown etiology. PM is characterized by muscle inflammation, proximal muscle weakness, and elevated muscle enzymes. The definitive diagnosis of PM is by histopathological examination (HPE). The role of imaging is complementary. Here, we present a case of PM showing intense muscle uptake both on 99m Tc-MDP bone scan and 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET CT). Objective: To highlight the role of 18F-FDG PET CT and 99m Tc-MDP bone scan in detecting inflammatory myopathies. Case History: A 37-year-old male patient came with the chief complaints of muscle weakness, muscle pain, and fever for 20 days. He was unable to sit from supine position and unable to stand from sitting position. He had a history of head drop. There was no history of dysphagia or respiratory fatigue. His creatinine kinase is 2106 IU/L, C-reactive protein is positive, erythrocyte sedimentation rate is 12 mm/1st H, and alkaline phosphatase is 63 IU/L. His antinuclear antibody profile was normal and is negative for anti-pANCA, anti-cANCA, and anti-GBM antibodies. The patient was referred to the Department of Nuclear Medicine for bone scan, in which there was diffuse intense tracer concentration in all the muscles symmetrically involving both sides, more predominant in proximal compared to distal muscles. The patient was suspected to be PM and suggested 18F-FDG PET CT, which also showed diffuse intense muscle uptake in all the muscles, predominantly in the neck muscles, paraspinal muscles, and proximal and distal muscles of upper and lower limbs. The subsequent HPE of muscle biopsy revealed inflammatory myopathy. Conclusion: In spite of the fact that final diagnosis of PM is by HPE, 99m Tc-MDP bone scan and 18F-FDG PET CT can be a useful adjunct to normal clinical and biochemical evaluation, especially to know the pattern of involvement of muscles, as both are whole-body imaging techniques.
| Nephro-urology Track | | |
| PP7: Comparison of glomerular filtration rate calculated by Gamma camera-based Gates method with various estimated glomerular filtration rate methods | | |
Manishi L. Narayan, Sanchay Jain, Ashok Kumar, Vandana Dhingra
Department of Nuclear Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
Background and Objectives: Glomerular filtration rate (GFR) is the best parameter to assess functional status of kidneys. Various equations have been devised to estimate the GFR indirectly using different patient indices. Among nuclear medicine methods, plasma sampling method is the most accurate for estimation of GFR; however, Gamma camera-based method using 99mTc-DTPA is used widely as it is noninvasive and easily available. Recently, the estimated GFR (eGFR) methods are gaining worldwide acceptance for quick estimation of GFR using serum creatinine and patient indices. The aim of this study was to compare Gamma camera-based Gates method with eGFR methods (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], Modification of Diet in Renal Disease [MDRD], Cockcroft Gault [CG]) of GFR estimation. Materials and Methods: We retrospectively reviewed records of 86 patients referred for 99mTc-DTPA scan (standard renogram). The mean age of patients included in the study was 45.9 ± 16.9 years, and serum creatinine values of these patients ranged from 0.17 to 12.16 mg/dl with average creatinine value of 3.25 mg/dl. Patients were divided into three subgroups according to the GFR calculated by Gates method as GFR <30 ml/min, 31–60 ml/min, and >61 ml/min. We then compared the eGFR methods using CKD-EPI method, MDRD method, and CG equation with Gates method of GFR estimation using 99mTc-DTPA in each subgroup. Results and Conclusions: In all patients, CKD-EPI best correlated with Gates method (r = 0.826, P < 0.001). However, at GFR <30 and >61 ml/min, CKD-EPI best correlated with Gates method (r = 0.62, P = 0.003 and r = 0.42, P = 0.004, respectively) while at GFR of 31–60 ml/min CG equation best correlated with Gates method (r = 0.52, P = 0.015) [Table 1]. Hence, CKD-EPI best correlates with GFR calculated with Gates method overall and at <30 and >60 ml/min in this study.
Keywords: 99mTc DTPA, Chronic Kidney Disease Epidemiology Collaboration, Cockcroft Gault, Gamma camera, glomerular filtration rate, Modification of Diet in Renal Disease
| PV11: Impact of different background regions of interest in the measurement of differential renal function in pediatric diuretic renogram | | |
Muhammad Junaid, Madhusudhanan Ponnusamy
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Objectives: Diuretic renography is performed to estimate differential function and to rule out obstruction in children with hydronephrosis. Different regions of interest (ROI), namely subrenal ROI, suprarenal ROI, and perirenal ROI, are used in background correction for the measurement of differential function. We compared differential function measured with the three background methods. Materials and Methods: We retrospectively collected data of 45 randomly selected patients under the age of 14 years who underwent diuretic renography between February 2018 and May 2018. All the patients had undergone 99mTc-L,L ethylene dicysteine and furosemide (F0 protool) on a Gamma camera equipped with low-energy high-resolution collimator. The images were acquired on 64 × 64 matrix, 1 s/frame for 1st min and 15 s/frame for 20 min. ROI were drawn around the kidneys and differential function was noted down with background correction using subrenal ROI, suprarenal ROI, and perirenal ROI. Comparison of differential function obtained by the three methods was done by paired t-test. Differential function between patients aged less than or equal to 2 and more than 2 were compared for each method using Mann–Whitney U-test. Results: The mean age of patients was 2.38 years (standard deviation [SD] 3.37). Mean differential function of left kidney estimated by subrenal, suprarenal, and perirenal background ROI was 51.9 (SD 10.3), 55.9 (SD 12.9), and 52.64 (SD 10.65), respectively. Complementary values were obtained for the right kidney. No significant difference was noted between the differential functions measured by perirenal and subrenal background ROI (P = 0.264). Paired t-test showed significant difference between the differential functions measured by suprarenal ROI and either of perirenal and subrenal background ROI (P = 0.03 and P = 0.02, respectively). There was no significant difference in differential function of patients aged less or equal to 2 and 2–14 years calculated for either of the three background correction methods. Conclusion: Perirenal and subrenal background correction methods provide similar differential renal function in children. Suprarenal background correction method revealed significantly different differential function values when compared to the other two methods. Differential function obtained by all the three methods of background correction was not affected by age.
| PV12: Comparison of double plasma sample method with single plasma sample methods in estimating glomerular filtration rate using radionuclides | | |
R. Ruth, Ajit S. Shinto1, S. Arun Pandiyan1, E. R. Radhakrishnan1, V. J. Arnold1, F. R. Kingsley1, B. Surya1, K. K. Kamaleswaran1, Raghi P. Jose1
KMCH Institute of Allied Health Sciences, 1Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
Background and Objectives: Glomerular filtration rate (GFR) is the most important parameter for the assessment of renal function; it estimates how much blood passes through the glomeruli each minute. The normal range is 80–120 ml/min .The ideal GFR estimation is with inulin clearance which remains the gold standard; there are different methods for determining GFR. In this study, we compare the double plasma sample method (DPSM) with single plasma sample method (SPSM) whether SPSM can replace DPSM. Materials and Methods: Forty adult renal donor patients were randomly selected. DPSM and SPSM estimated GFR value were compared and correlated using Pearson correlation. Plasma Sampling Method: Standard dose with 1 mCi in 1 ml is taken and weighed and patient dose with 1 mCi in 1 ml is taken and weighted and then injected intravenous to the patient and blood samples of about 3 ml are obtained in the contra lateral hand at 120 min and 240 min respective to SPSM and DPSM. Then, the blood samples are centrifuged at 3000 rpm for 10 min and both the samples of plasma about 1 ml are counted individually for 60 s along with standard dose. Results and Conclusion: There is reasonable concordance between the DPSM and single sample method based on preliminary evaluation.
| PV13: Evaluation of quantitative parameters on renography in antenatally diagnosed hydronephrosis | | |
Suchismita Ghosh, Venkatesh Rangarajan, Ameya D. Puranik, Nilendu Purandare, Archi Agrawal, Sneha Shah
Tata Memorial Hospital, Mumbai, Maharashtra, India
Background and Objectives: With the increasing use of antenatal ultrasonography (USG), many congenital abnormalities are often picked up in utero, of which antenatally detected hydronephrosis is the most common. Diuretic renography can be a useful tool to differentiate between obstructed and unobstructed hydronephrosis. We evaluated the results of Tc99m EC renogram in 40 patients with antenatally diagnosed unilateral/bilateral hydronephrosis on USG in the age group of 1 month to 2 years. The aim of the study was to assess the quantitative parameters such as time to half peak and split renal function and establish relation to the postnatal management. Materials and Methods: A total of 38 patients in the age group of 1 month to 2 years with antenatally detected unilateral/bilateral hydronephrosis on USG underwent Tc99m EC renography (F0 protocol). Split function and T1/2 after diuretic stimulation on background subtracted renographic curves were used as criteria to comment upon the drainage. A T1/2 of >20 min was taken to be obstructed drainage. A follow-up was maintained so as to know what management was offered to these patients. The follow-up included either a repeat USG or renogram after 3 months or any surgical procedure such as pyeloplasty or nephrectomy. Results: Seventeen out of 38 patients with obstructed drainage, i.e., T1/2 >20 min, were operated upon (pyeloplasty, 1 underwent nephrectomy) out of which only five had SRF <30%, rest had SRF in the range of 45%–55%. Fifteen patients with progressive drainage were kept on follow-up with an USG or EC renogram after 3–6 months from the previous scan. Remaining six patients had absolutely normal drainage and function. Conclusion: Diuretic renography is a useful tool in postnatal management in patients with antenatally diagnosed hydronephrosis to differentiate between obstructed and unobstructed drainage. It can also be used as a decision-making tool for whether to operate or just follow-up the patients with obstructed drainage.
| PV14: Cortical transit time: Can it be a sole parameter to predict the need for surgery in hydronephrosis in pediatric population? | | |
Melvika Pereira1, Madhuri Shimpi Mahajan1,2, Natasha Singh1
1Department of Nuclear Medicine, P. D. Hinduja National Hospital and MRC, Mahim, 2Department of Nuclear Medicine, Lilavati Hospital and Research Centre, Bandra, Mumbai, Maharashtra, India
Background and Objectives: Most cases of antenatal hydronephrosis need not require surgery. However, the key issue is to identify those patients who will benefit from pyeloplasty, secondary to obstructive etiology and whose function will deteriorate or improve according to whether they undergo surgery or not. Among conventional tools, none have given a good reliable prognostic marker whereas cortical transit time (CTT) has been suggested to successfully predict renal function deterioration in nonsurgically treated pelviureteric junction obstruction (PUJO). We thus retrospectively evaluated whether initial CTT significantly correlated with need for surgery in pediatric hydronephrosis population. Materials and Methods: Forty patients underwent Tc99m DTPA diuretic renogram in the period (June 2011–February 2015) and their CTT was studied visually (normal: 2.5–3 min). All patients were followed up. Results: Of total 40 patients, four had normal scans. Sixteen of 40 patients had normal CTT and showed functional excretory delay, hence managed conservatively, and showed normal ultrasound on follow-up. Twenty of 40 patients showed PUJO, of which 16 had abnormal CTT and underwent pyeloplasty, with functional improvement on follow-up in 15 and no deterioration in 1. Remaining four had normal CTT of which one underwent pyeloplasty due to other kidney being dysplastic. Sensitivity of CTT to predict the need for surgery was 94.12% (95% confidence interval [CI]: 71.31%–99.85 %), and specificity 100% (95% CI: 29.84%–100%). Conclusion: CTT could be a reliable prognostic parameter to determine need for surgery and future evolution of renal function in children with hydronephrosis.
| Neurology Track | | |
| OP12: Evaluation of amnestic mild cognitive impairment using 18F-AD-ML-104 Tau positron emission tomography/computed tomography | | |
Jasim Jaleel, Madhavi Tripathi, Vivek Baghel, Praveen Kumar, Nishikant A. Damle, C. S. Bal, A. B. Dey1, Gaurav Desai1
Departments of Nuclear Medicine and 1Geriatric Medicine, AIIMS, New Delhi, India
Background and Objectives: Mild cognitive impairment represents an intermediary condition between normal cognition and clinically overt dementia. An early identification of patients with mild cognitive impairment, who may progress to Alzheimer's dementia (AD) or other types of dementia, provides a window of opportunity for early intervention and future prognostication. The objective of the study is to evaluate the 18F-AD-ML-104 Tau spatial distribution pattern in mild cognitive impairment. Materials and Methods: Fifteen patients (n = 15) clinically diagnosed as mild cognitive impairment underwent 18F-FDG positron emission tomography (PET) and 18F-AD-ML-104 Tau PET scan. Patients were divided into two groups based on the presence of Alzheimer's pattern of hypometabolism on the 18F-FDG PET scan. Regions of interest were drawn over both frontal, parietal, lateral temporal, medial temporal, precuneus, and posterior cingulate cortices and the cerebellum. Tau retention in the two groups was calculated using SUVR (region/cerebellum) and compared using Mann–Whitney U-test. Results: Maximum 18F-AD-ML-104 Tau retention was noted in the medial temporal lobes in both groups (SUVR=1.77 in hypometabolism-positive group) and (SUVR=1.43 in hypometabolism-negative group) (P = 0.16). Significant difference in Tau retention between groups was noted in both lateral temporal (P = 0.05), posterior cingulate (P = 0.02), and precuneus (P = 0.01) cortices. Conclusion: We could thus demonstrate a significant difference in tau retention in patients with AD pattern of hypometabolism on FDG PET in the lateral temporal, posterior cingulate, and precuneus cortices compared to the patients whose FDG PET was unlikely of progression to AD, suggesting its utility as a biomarker for AD.
[TAG:2]OP13: Neuroimaging of glioma recurrence versus radiation necrosis: Using 99mTc MDM (bis-methionine-DTPA) single-photon emission computed tomography and comparison with dynamic susceptibility contrast-enhanced-magnetic resonance imaging and magnetic resonance spectroscopy and clinical findings[/TAG:2]
Nisha Rani, B. Singh, N. Kumar1, P. Singh2, P. Hazari3, A. Jaswal3, A. K. Mishra3, A. Bhattacharya, A. Kohli4, S. Gupta5
Departments of Nuclear Medicine, 1Radiotherapy, 2Radio diagnosis and Imaging, 4Psychiatry and 5Neurosurgery, PGIMER, Chandigarh, 3Division of Cyclotron and Radiopharmaceutical Sciences and PET Centre, INMAS, DRDO, Delhi, India
Background and Objective: In this study, 99mTc MDM (bis-methionine-DTPA) single-photon emission computed tomography (SPECT) was used for the detection of recurrent glioma from radiation necrosis and the results were compared with dynamic susceptibility contrast-enhanced (DSCE)-magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and clinical findings. Materials and Methods: This prospective study enrolled 23 patients (9 females and 14 males). All cases initially presented with histologically proven glioma and underwent surgical intervention followed by radiotherapy (+/-chemotherapy). All the patients underwent 99mTc-MDM SPECT/CT, DSCE-MRI, and MRS imaging and evaluated for recurrent/necrosis lesion. The target (lesion) to nontarget (T/NT) ratio was evaluated for MDM-SPECT and SPECT/MR fusion was done by appropriate software (Multimodality Oasis Server version 1.9.4.3, Segami Corp.). Relative cerebral blood volume (nCBVmax) maps were calculated using perfusion analysis software (Nordic NeuroLab, Bergen, Norway) and signal intensities of choline (Cho), total creatine (Cr), N-acetyl aspartate (NAA), and lipids-lactate (LL) were analyzed to calculate Cho/Cr, Cho/NAA, and Cho/LL ratios. Results: In the present study, visual 99mTc MDM SPECT/CT, DSCE MRI (mean follow-up of 21 months), and MRS interpretation, quantitative image analysis, and clinical findings were considered for making the final diagnosis of recurrent disease in 13 patients and radiation necrosis in10 patients. We found a clearly defined hotspot in MDM-SPECT scan in 13/23 patients with recurrent disease and DSCE-MRI showed concordant with MDM-SPECT results and regions with nCBVmax corresponded with hotspot regions in all 13 cases of recurrence. T/NT and metabolite ratios (Cho/NAA, Cho/Cr) disagreed in six patients. Cho/LL ratio disagreed with methionine uptake in 8 patients (4/13 were false negative and 4/10 were false positive). These five (T/NT, nCBVmax, Cho/NAA, Cho/Cr, and Cho/LL) quantitative ratios achieved an acceptable balance between sensitivity and specificity for distinguishing recurrent tumor to radiation necrosis and each ratio defined a cutoff for diagnosing recurrent tumor. The ratios are as follows: T/NT> 1.75 (sensitivity 93% and specificity 88%), nCBVmax >1.97 (sensitivity 86%, specificity 88%), Cho/NAA >1.14 (sensitivity 86%, specificity 75%), Cho/Cr >1.33 (sensitivity 80%, specificity 75%), and Cho/LL >.93 (sensitivity 69%, specificity 60%). A positive association between the T/NT and nCBV, Cho/NAA, and Cho/Cr was observed (r = 0.75, 0.65, and 0.53, respectively, at P = 0.01). Association of T/NT with Cho/LL ratio was not statistically significant. Conclusion: 99mTc MDM SPECT/CT and DSCE-MRI demonstrated more accurate compared to MRS for the detection of tumor recurrence in glioma patients. Furthermore, this study revealed that co-registered MDM-SPECT and MRI facilitates for identification of regions with recurrence.
| PP8: Evaluation of effect of spinal trauma on brain metabolism using 18F-labeled fluoro-2-deoxyglucose positron emission tomography using statistical parametric mapping | | |
Abhinav Jaimini, Maria M. D'souza, Rajnish Sharma
INMAS, Delhi, India
Background and Objectives: The relevance of loss of sensorimotor function for the reorganization of cerebral sensorimotor systems is not well-understood postspinal trauma. Clinical and neurophysiological studies provide evidence for reorganization of the primary motor and sensory cortex in patients with spinal cord injury or amputees. However, the relation between cerebral reorganization within these regions and neuronal activity of functionally associated brain areas is not imaged. In the present study, we used PET and the tracer 18F-fluorodeoxyglucose to study regional cerebral glucose metabolism in cases with spinal trauma. Materials and Methods: PET and 18F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in six patients with spinal cord injury and compared with 19 healthy subjects. Statistical parametric mapping (SPM 5) was applied to compare both groups on a pixel by pixel basis (significance level P = 0.05). Results and Conclusion: SPM analysis showed relatively increased glucose metabolism particularly in bilateral supplementary motor area, right middle cingulate, bilateral superior frontal gyrus, and left temporal gyrus. Maximal relatively reduced glucose metabolism in patients with spinal cord injury was found in the right fusiform gyrus, left lingual gyrus, right precuneus, right lingual gyrus, left superior parietal lobule, right middle occipital gyrus, and left caudate. Thus, the results show remodeling of brain functional areas postspinal trauma. Relatively increased glucose metabolism in the brain regions involved in attention and initiation of movement may be related to secondary disinhibition of these regions.
| PP9: To assess the role of fluoro-2-deoxyglucose positron emission tomography/computed tomography in the evaluation of focal cortical dysplasia in patients with intractable epilepsy | | |
A. S. Rahul, Shwetal Pawar1
NBE, New Delhi, 1Seth GSMC and KEMH, Mumbai, Maharashtra, India
Background and Objectives: Focal cortical dysplasia (FCD) includes a wide spectrum of gray and white matter anomalies of the brain that range from mild cortical disruption to complete derangement of neocortical lamination (Taylor's FCD). The purpose of the study was evaluate the ability of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG-PET) to detect the dysplastic cortex, to localize the epileptogenic zone (EZ), and to improve the surgical outcome in patients with FCD. This study investigates the usefulness of 18F-FDG PET/CT in the evaluation of FCDs and to correlate 18F-FDG uptake qualitatively. Materials and Methods: A retrospective plus prospective study was done on 15 patients with intractable epilepsy with their magnetic resonance imaging (MRI) revealing FCD. Patients underwent 18F-FDG PET/CT of the brain and the uptake of 18F-FDG was assessed visually on the PET image slice, which was matched with the MRI slice of the lesion. Regions of decreased uptake were correlated with the MRI scan and the efficiency of 18F-FDG PET/CT in detecting the pathology seen in MRI was assessed. Results and Conclusion: Chi-square test was performed to compare the 18F-FDG hypometabolism and the MRI defined lesion. Chi square test yielded a significant result. All P values were tested and significance was set at a P < 0.005 and likelihood ratio was less than 0.024 (version 17.0; SPSS Inc.). 18F-FDG PET/CT detected the pathology in 10 patients (66.7%) and normal metabolism was found in five MRI positive patients (33.3%). Mean SUVmax of PET detected FCD patients (10 patients) were 5.02 (mean SUVmax of normal brain was found to be 9.70) in which four patients showed more extend of disease than seen in MRI and six patients showed lesion same as that detected in MRI. moreover, nine patients (60%) did not undergo surgery where PET/CT findings assisted decision-making.
| PP10: (99m)Tc-TRODAT-1 single-photon emission computed tomography and (18)F-FDOPA positron emission tomography in clinically suspected Parkinson's disease | | |
Vivek Baghel, Madhavi Tripathi, Nishikant Avinash Damle, Harish Goyal, Praveen Kumar, Geetanjali Arora, Ansul Sharma, Vinay Goel1, Chandra Sekhar Bal
Departments of Nuclear Medicine and 1Neuroradiology, All India Institute of Medical Sciences, New Delhi, India
Background and Objectives: The current study aimed to assess the correlation between dopamine transporter imaging (DAT) using Tc-99m-TRODAT-1 single-photon emission computed tomography (SPECT)/CT (TTDS) and FDOPA PET/CT in patients with clinically suspected Parkinson's disease (PD). The usual protocol followed in our department is to do TTDS to confirm presynaptic dopaminergic dysfunction (PSDD) in patients referred with parkinsonism. This is followed by FDOPA PET/CT in those cases where the reporting physician was not confident in reporting the TTDS and further correlation was felt useful. Materials and Methods: We undertook this retrospective review in 32 patients with clinical suspicion of PD who underwent both 99m Tc-TRODAT-1 SPECT/CT scan and (18)F-FDOPA PET/CT scan in our department between 2014 and 2018. SPECT images were acquired 4 h after intravenous injection of 20–25 mCi of Tc-99m TRODAT, followed by CT acquisition on Symbia T6 dual-head Gamma camera (Siemens). Brain PET images, 3D emission scans of 15 min were acquired 60 min after injection of 5 mCi of FDOPA intravenously on a BiographmCT (Siemens) PET/CT scanner. Both scans were visually interpreted; SPECT scans before the PET scans and each independent of the other. Consensus was sought where interpretations differed. All the patients were telephonically interviewed to assess clinical outcome and treatment at a follow-up that ranged from 6 months to 4 years. Results: A concordant result between TTDS and FDOPA PET/CT was obtained in 27/32 patients (84%). 24 of these patients (89%) with concordance on both modalities concurred with the clinical diagnosis and this included 17 patients with PD and 7 with nonneurodegenerative parkinsonism. In the remaining three patients (11%), the imaging diagnosis did not concur with the clinical follow-up. Discordant results were seen in 5/32 patients (16%). Of these in two cases (6.3%), the SPECT results concurred with the clinical follow-up while in the other 3 cases (9.3%), PET correlated better with the clinical follow-up. Conclusion: Concordance of TTDS and FDOPA PET/CT with each other and the clinical diagnosis is good so TTDS as a single investigation is useful to evaluate PSDD that characterizes PD. When the two modalities are discordant FDOPA PET correlates better with the clinical outcome.
| PV15: Utility of 18F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography in diagnostic workup and response evaluation in a case of neurosarcoidosis | | |
K. B. Sricharan, R. Ramya Priya, Ranadheer Mantri, B. Vengamma, A. Y. Lakshmi, Tekchand Kalawat
SVIMS, Tirupati, Andhra Pradesh, India
Background and Objective: 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F FDG PET/CT) is a noninvasive molecular imaging test with inbuilt feature of whole-body survey, often useful in situations, where the diagnosis based on clinical findings, results of routine serological, radiological, and biochemical tests are difficult. We report a case of 59-year-old female presented with fever and neurological signs and symptoms. She underwent 18F FDG PET/CT scan, which showed interesting findings and utility in management of patient. The present study aims to evaluate the utility of 18F FDG PET/CT scan in diagnostic workup and treatment response evaluation in a case of neurosarcoidosis. Case History: A 59-year-old female presented with fever, headache, arthralgia, and weakness of both lower limbs since 2 months. Routine blood investigations showed raised erythrocyte sedimentation rate (40 mm in 1st h), positive serum ANA, and normal serum ACE levels. Cerebrospinal fluid analysis was negative for TB/viral meningitis and malignant cells. Magnetic resonance imaging brain and dorsal spine showed focal dural thickening below the foramen magnum and heterogenous patchy enhancement of soft tissue along with bulky cord from D-9 to L-1 vertebrae, respectively. With these findings, the patient was suspected for idiopathic hypertrophic pachymeningitis/neurosarcoidosis. For further histopathological evaluation (HPE), patient was not willing for cord biopsy and advised for 18F FDG PET/CT scan with an intention to localize any other metabolically active potential site for HPE. 18F FDG PET/CT showed intense FDG concentration in spinal cord, at the corresponding site of MRI lesion extending from D9 to L1 vertebrae with maximum SUV of 6.1 with no other focal abnormal FDG concentration noted in the body. Based on the clinical examinations, laboratory tests, and imaging findings, she was diagnosed as a case of neurosarcoidosis and treated with prednisolone orally in dosage of 1 mg/kg per day. In view of persistence of cord thickening, azathioprine 50 mg/day was started. During the course of treatment, the patient responded and recovered completely. A follow-up 18F FDG PET/CT scan was performed after 2 months, which revealed complete resolution of metabolically active lesion in spinal cord, as localized in pretreatment scan. Conclusion: In inflammatory of unknown origin presenting with neurological features, 18F FDG PET-CT can not only aid in knowing the extent of disease detecting any biopsiable site but also help in the evaluation of response.
| PV16: Pictorial essay of neurological indications of positron emission tomography-computed tomography: An institutional experience | | |
Surekha Yadav
Department of Nuclear Medicine, Army Hospital, Research and Referral, New Delhi, India
Background and Objective: This presentation focuses on the potential of advanced applications of functional molecular imaging in assessing certain neurological conditions diagnosed and followed up in the institution from the Department of Neurological Sciences. Discussion: Few cases in the pictorial essay are (i) Rasmussen encephalitis, (ii) moyamoya disease, (iii) progressive supranuclear palsy, (iv) MSA-P, (v) progressive retrograde dementia, and Alzheimer's, (vi) pituitary adenomas, and (vii) paraneoplastic syndromes. The cases were identified and routine investigations along with biopsy, cerebrospinal fluid analysis, magnetic resonance imaging, and PET-CT were carried out at the institutional level. We followed up these cases. They underwent treatment (medical/surgical) along with response assessment PET-CT scans. Results and Conclusion: The PET-CT findings will be analyzed and presented in the light of existing literature.
| PV17: Rasmussen's disease fluoro-2-deoxyglucose positron emission tomography-computed tomography as a complementary role in neuroimaging | | |
Anurag Jain, Abhishek Mahto, Arun R. John, M. G. Vishnoi, A. G. Pandit, K. P. Solanki, Braj Kishore
Department of Nuclear Medicine, Army Hospital R and R, Delhi, India
Background and Objective: Rasmussen's encephalitis (RE) is rare inflammatory neurodegenerative disease usually affecting single cerebral hemisphere. It manifests as progressive neurological deterioration and intractable seizures. Imaging plays a vital role in the diagnosis. Results and Conclusion: The diagnosis of RE is clinically challenging and based on exclusion in patients with intractable seizures and progressive motor cognitive deterioration. Epilepsy surgery has a major role in RE and it remains the curative treatment for disease progression and has achieved wide range of seizure control. Due to refractory and progressive disease, the treatment options are disconnective techniques such as functional hemispherectomy (resection of affected cerebral hemisphere sparing frontal and occipital lobe) and hemispherotomy, to achieve seizure control. Thus, as a guiding tool for definitive surgical intervention, particularly in cases of nonspecific clinical findings, anatomical neuroimaging and metabolic neuroimaging are of critical importance. A lateralization of diffuse unilateral hypometabolism in 2-deoxy-2(18F)fluoro-D-glucose positron emission tomography computed tomography (FDG PET CT) and corresponding equivalent region of cerebral atrophy on magnetic resonance images supports the diagnosis of RE and gives precise information on the metabolic extent of disease. FDG PET CT has got a potential benefit in this to localize and lateralize the seizure focus. Here, we report four cases of RE in which FDG PET CT showed varied distribution of disease and proved an added benefit in neuroimaging. FDG PET CT shows a characteristic pattern of asymmetrical cerebral atrophy with ipsilateral hypometabolism and contralateral cerebellar atrophy associated with hypometabolism, i.e., crossed cerebellar diachiasis, probably due to propagation of seizure activity along corticopontocerebellar pathway.
| Oncology Track | | |
| OP14: Brain tumors imaging with copper-64 chloride: Feasibility and early experience | | |
Sanjay Gambhir, Vipin Kumar, Manish Ora, Subhash Chand Kheruka
Department of Nuclear Medicine, SGPGIMS Lucknow, Uttar Pradesh, India
Background and Objectives: Copper transporter receptors (CTRs) have been postulated to be present only in high-grade brain tumors/glioma. This knowledge obtained from imaging with copper will further help to choose potential candidate for theragnostic therapy with other copper isotopes. We report preliminary evidence of 64CuCl2 uptake in various grades of brain tumors to aim toward this goal. Materials and Methods: A prospective study was done on patients presented with suspected brain tumors based on magnetic resonance imaging (MRI) finding. After taking informed consent all patients were administered copper-64 chloride (64CuCl2, ~175 MBq) and brain positron emission tomography (PET)/computed tomography (CT) imaging was performed at 2 and 24 h after administration. Standardized uptake values (SUVs) were calculated. After imaging, all patients advised for surgery and 64CuCl2 PET/CT imaging findings were correlated with MRI and histopathological evaluation (HPE). Results: A total of 10 patients have been enrolled till now. Out of 10 patients, MRI was suggestive of high-grade brain tumor in 7, low grade in 2, and meningioma in 1 patient. Five out of ten patients showed 64CuCl2 uptake on PET/CT with variable SUVmax (1.4–20). HPE were suggestive of low-grade astrocytoma (SUVmax-1.4 and 3.5 at 2 and 24 hours), pilocytic astrocytoma (SUVmax 3.8 and 1.5 at 2 and 24 h), anaplastic astrocytoma (SUVmax 11.1 and 20.0 at 2 and 24 h), meningothelial meningioma (SUVmax 10.3 and 5.17 at 2 and 24 h), and atypical meningioma (SUVmax 2.4 and 1.3 at 2 and 24 h). In five patients with no uptake on PET CT, HPE revealed anaplastic oligoastrocytoma and oligodendroglioma in two patients. For rest of the three patients, HPE is not available till date. Conclusion: This preliminary study suggests that 64CuCl2 is accumulating in some but not all high-grade brain tumors. There appears to variability in the grade of copper uptake in all grades of tumors. More data are being cumulated to define the cutoff of copper uptake as potential differentiating features for identifying possible theragnostic targets.
| OP15: Implications of fluoro-2-deoxyglucose uptake in low-intermediate-grade metastatic neuroendocrine tumors from PRRT outcome viewpoint: A semi-quantitative SUV-based analysis | | |
Aadil Adnan
Radiation Medicine Center, BARC, Mumbai, Maharashtra, India
Background and Objectives: Dual tracer positron emission tomography (PET) imaging approach (with 68Ga-DOTATATE PET-computed tomography [CT] for SSTR and 18F-labeled fluoro-2-deoxyglucose [18FDG] PET-CT for GLUT receptor) plays a vital role in baseline differentiation, treatment decision-making, and prognostic assessment of neuroendocrine tumors (NETs). The study aims to observe and compare the clinical behavior of low/intermediate-grade NETs depending upon their baseline FDG metabolism (calculated through pre-PRRT FDG SUV) and to determine its prognostic importance in predicting extent of therapeutic response (post-PRRT) in terms of symptomatic, biochemical, and scan parameters along with the long-term impact on progression-free and overall survival (PFS and OS). Materials and Methods: Fifty-nine patients with low (≤2%) and intermediate (3%–20% Mib 1/Ki-67 index) grade metastatic NET were selected for this retrospective analysis and divided into three groups: Group 1 consisted of patients having low-grade FDG uptake at baseline, pre-defined as SUVmax <5 (n = 13); Group 2 consisted of those having intermediate-grade FDG uptake at baseline, SUVmax 5–10 (n = 34) and Group 3 consisted of patients having high-grade FDG uptake at baseline, defined as SUVmax >10 (n = 12). The trend of FDG avidity was studied from the baseline till the time of analysis and the overall outcomes were compared in terms of symptomatic response (Karnofsky and ECOG performance score), biochemical response, scan response (anatomical and metabolic, RECIST 1.1 and PERCIST 1.0), PFS, and OS. Results: Patients in Groups 1 and 2 showed highest proportion of symptomatic complete response (CR), biochemical partial response (PR), and stable disease (SD) on scan. These patients also demonstrated better PFS and OS and lowest hazard ratio compared to patients in the Group 3. An important finding was a substantial fraction of the complete metabolic responders (CMRs) across the groups (85% of Group 1, 51% of Group 2, 47% of Group 3), achieved CMR within first two cycles of PRRT. Conclusion: Most of the patients of low/intermediate grade NET having low to moderate baseline tumor FDG metabolism (SUVmax ≤10) showed favorable symptomatic response with good biochemical and anatomical disease control and were associated with prolonged PFS and OS, compared to that of those having high-grade baseline tumor FDG metabolism (SUVmax >10).
| OP16: Diagnostic accuracy of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in mediastinal lymph nodal staging of recently diagnosed carcinoma lung | | |
Ramkumar
Sir Ganga Ram Hospital, New Delhi, India
Background and Objectives: Mediastinal lymph nodal staging is important for deciding the treatment and predicting the prognosis of the recently diagnosed carcinoma lung patients. The aim of this study is to evaluate the diagnostic accuracy of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (F-18 FDG PET/CT) in mediastinal lymph nodal staging in carcinoma lung patients. Materials and Methods: A total of 120 recently diagnosed lung carcinoma patients (95 males, 25 females; mean age 58.9 ± 11.39 years) who underwent pretreatment F-18 FDG PET/CT for staging between March 2016 ane May 2018 were included in the study. Eleven patients had pulmonary tuberculosis in the past and five patients had history of empirical ATT. Lymph nodes with size more than 1 cm in short axis and SUV maximum more than 3.0 in F-18 FDG PET/CT scan were considered as suspicious for metastasis and correlated with their histo/cyto-pathological reports. Various parameters such as age, sex, tuberculosis history, ATT history, and number of mediastinal lymph nodes sampled in each station were recorded. Clinical TNM staging assessed with PET/CT was compared with pathological TNM staging. The data were analyzed using appropriate statistical methods. Results: A total of 560 lymph node stations with a mean of 4.6 lymph node stations per patient and total of 3117 lymph nodes with a mean of 25.9 lymph nodes per patient were resected. 179 nodes were reported positive with metastases and 37 nodes were reported as granulomatous. Level 10 was the most common station involved. FDG PET/CT staged 68 (56.7%) patients as N0, 18 (15%) as N1, 28 (23.3%) as N2, and 6 (5%) as N3. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET CT in staging lung cancer patients were 79.5%, 77.63%, 67.3%, 86.76%, and 78.3%. The overall per nodal station basis sensitivity, specificity, positive predictive value, negative predictive value, and accuracy was 51.2%, 98.3%, 84%, 92.2%, and 91.4%. On comparing N staging on PET CT with pathological N staging, 85 (70.8%) patients were staged accurately, 22 (18.3%) were over-staged, and 13 (10.8%) were under-staged. Conclusion: F-18 FDG PET CT is a fairly accurate imaging modality for mediastinal lymph nodal staging in carcinoma lung patients. However, in view of low sensitivity and low positive predictive value, which may be attributed to limited spatial resolution of the PET scanner and high granulomatous disease burden in the country, it is not an alternative to pathological staging in these patients.
| OP17: Initial experience with 18F-fluoroglutamine positron emission tomography/computed tomography imaging for tumor response assessment in cerebral gliomas | | |
Reema Goel, Kwaku Domfe1, Alexandra Miller2, Elena Pentsova2, Viviane Tabar2, Ingo Mellinghoff2, Christian Grommes2, Lisa DeAngelis2, Maya Graham2, Robert Young, Mark Dunphy
Departments of Radiology and 2Neurology, Memorial Sloan Kettering Cancer Center, 1College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
Background and Objectives: Differentiating true tumor progression from treatment induced necrosis in glioma is a central challenge in neuro-oncology. Positron emission tomography (PET) tracers such as FDG, FET, and MET and combination of various MR parameters such as MRS, DWI, and MR perfusion have been individually evaluated for this purpose. The aim of this study was to assess the clinical value of a novel PET tracer, 18F-flouroglutamine in differentiation of progression from post treatment changes in gliomas. Materials and Methods: 20 patients (2 low-grade and 7 high-grade astrocytomas, 1 anaplastic oligodendroglioma, 1 anaplastic ependymoma, and 9 glioblastoma multiforme) with suspected recurrence or equivocal findings on MRI underwent 18F-fluoroglutamine PET/CT imaging before the start of new treatment (7), within 12 weeks after completion of radiochemotherapy (10), and after 12 weeks post completion of radiation therapy/chemoradiation (3). Ten patients also underwent 18F-FDG PET/CT. Qualitative and quantitative evaluation (maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) was performed. Reference standard was based on the clinical course, follow-up MR imaging, and/or histopathological findings. Results: 18F-Fluoroglutamine PET showed sensitivity of 94% and specificity of 67% in differentiating tumor progression/presence of high-grade glioma (true positive = 16; false positive = 1; true negative = 2; false negative = 1).Of 10 patients classified as having early true progression, eight were positive on fluoroglutamine and of two patients classified as true late progression both were positive on fluoroglutamine. Conclusion: 18F-fluoroglutamine PET may facilitate the diagnosis of early/late pseudoprogression following radiochemotherapy of cerebral gliomas.
| OP18: Positron emission tomography-based molecular imaging using tripeptide RGD for over expression of αvβ3 biomarker in various malignancies | | |
Rakhee Vatsa, Bhagwant Rai Mittal, Jaya Shukla, Sunil Kumar, Ashwin Singh Parihar, Gurpreet Singh1, Sudipta Chakraborty2, Ashutosh Dash2, Devinder K. Dhawan3
Departments of Nuclear Medicine and 1Surgery, Post Graduate Institute of Medical Education and Research, 3Centre for Nuclear Medicine, Panjab University, Chandigarh, 2Isotope Applications and Radiopharmaceuticals Division, BARC, Mumbai, Maharashtra, India
Background and Objectives: Overexpression of integrin αvβ3 is greatly associated with angiogenesis, a crucial process for growth and metastasis of tumors beyond 5 mm. RGD (arginine-glycline-aspartic acid) tripeptide-based molecular probes are used to target αvβ3 integrins which are overexpressed on various tumors ranging from carcinoma, sarcoma, to neuroendocrine tumors. The present study aims to evaluate Ga-68-labeled RGD peptide as a potential biomarker for imaging integrin αvβ3 overexpression in breast and lung carcinoma, glioma, and TENIS patients. Materials and Methods: Commercially available DOTA-RGD2 was radiolabeled with Ga-68 in-house in semi-automated fluidic module. Quality control tests were performed. The study was duly approved by the Institutional Ethics Committee and written informed consent was taken from all the patients. A total of 47 patients (25 of breast carcinoma, 10 lung carcinoma, 10 TENIS, and 2 GBM) were enrolled in the study, before start of any treatment. Whole-body images (regional in glioma) were acquired in 3-D mode 45 min postinjection of 3–5 mCi of Ga-68-DOTA-RGD2. The uptake of Ga-68-DOTA-RGD2 was assessed from a circular region of interest (ROI) over the entire lesion/lesions and expressed as the maximum standardized uptake value (SUVmax). Results: The average radiolabeling yield in all preparations was found to be greater than 95%. Radiochemical purity of purified product was >99%. Other quality control parameters including endotoxins (<3.7 EU/ml) and residual ethanol (<2500 ppm) content were well within the limits. All the samples were found to be sterile on sterility test. Physiological uptake of radiotracer was seen in ventricles, salivary glands, liver, and spleen with excretion through the kidneys. The SUVmax in breast lesions were ranging from 1.8 to 20.39. Few metastatic lesions were also noted in breast carcinoma patients. However, no Ga-68-DOTA-RGD2 uptake was observed in metastatic liver lesions. In lung carcinoma patients, the SUVmax for lung lesion ranged from 4.75 to 7.8. The SUVmax TENIS and glioma patients were ranging from 5.2 to 14.1 and 1.2 to 2.4, respectively. Conclusion: In-house preparation of Ga-68-DOTA-RGD2 demonstrated high radiochemical yield and good clinical efficacy. However, studies with more number of patients should be encouraged to validate the results in various tumors.
[TAG:2]OP19: Comparison of 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography and 18F-Fluorocholine positron emission tomography/computed tomography in restaging of adenocarcinoma prostate patients with rising serum prostate-specific antigen levels postprimary or adjuvant therapy[/TAG:2]
Sarthak Tripathy, Nishikant Avinash Damle, Chandra Sekhar Bal, Abhinab Singhal, Madhavi Tripathi, Rajeev Kumar, Praveen Kumar, Prabhjot Singh, K. P. Haresh, Geetanjali Aror
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: The objective of this study was to compare the accuracy of 68Ga-prostate-specific membrane antigen (PSMA)-HBED-CC positron emission tomography-computed tomography (PET-CT) (PSMA) with 18F-fluorocholine PET-CT (FCH) in restaging of patients with adenocarcinoma prostate who present with rising serum prostate-specific antigen (PSA) levels post initial therapy. Materials and Methods: Twenty-seven patients (age: 47–81 years, mean 65 ± 9 years) with a history of treatment for adenocarcinoma prostate underwent PSMA and FCH PET-CT within a span of 2 months. Serum PSA ranged between 0.22 and 212 ng/ml. Background corrected SUV ratios (SUVR) were calculated for both PSMA and FCH avid lesions. Comparison between the two radiotracers was done by lesion-wise and patient-wise analysis using IBM SPSS 20v software. Results: PSMA PET-CT detected lesions in 16/27 (59.2%) patients whereas FCH PET-CT detected lesions in 13/27 (48%) patients (P = 0.125). Eleven (11/27) patients were negative on both the scans. In total, PSMA PET/CT detected 275 lesions (230 skeletal, 31 lymph node, 11 in prostate bed, 3 in the liver) in total 16 patients; while FCH PET/CT detected 262 lesions (225 skeletal, 23 lymph nodes, 7 in prostate bed) in 13 patients(P = 0.01).Lesion detection rate of 68Ga-PSMA was significantly higher in lymph node and visceral lesions (P < 0.05) while the difference was insignificant in skeletal lesions (P = 0.102), when compared to FCH. SUVR of PSMA were greater than FCH for skeletal lesions (P = 0.237), lymph nodes (P = 0.018), and visceral lesions (P = 0.398). Subgroup analysis of patients according to their PSA levels revealed the results as shown in [Table 1]. Conclusion: 68Ga-PSMA PET-CT as a novel modality in evaluation of prostate cancer patients with biochemical relapse may be superior to the traditional 18F-FCH PET-CT, owing to its higher lesion detection rate particularly at lower serum PSA levels with better tumor-to-background contrast. Furthermore, it can identify the patients who would benefit from 177Lu or 90Y-based PSMA therapy.
| OP20: Role of F18 FDOPA positron emission tomography/computed tomography in differentiating the recurrent high-grade gliomas from the recurrent low-grade gliomas | | |
Anshul Sharma, Manmohan Singh1, Chitra Sarkar2, S. S. Kale1, Subhash Gupta3, K. P. Haresh3, Madhavi Tripathi, Chandra Sekhar Bal
Department of Nuclear Medicine, 1Neurosurgery, 2Pathology and 3Radiation Oncology, AIIMS, New Delhi, India
Background and Objectives: The prognosis of the patients with recurrent brain tumors depends upon the grade of the tumor and the proliferation index of the tumor cells. Both these parameters are obtained from the histopathology, which may not always be feasible. With this study, we tried to differentiate the high-grade glioma (HGG) from the low-grade glioma (LGG), using F18 FDOPA positron emission tomography-computed tomography (PET/CT). Furthermore, we tried to establish the relationship between the proliferation index (MiB%) and the semi-quantitative parameters from the PET/CT. Materials and Methods: 17 histopathologically proven cases of primary brain tumors underwent PET/CT 20 min after IV injection of 3–5 MBq/kg F18-FDOPA. Of these 16 were re-operated for recurrence and one underwent biopsy. Of 20 lesions identified, one was false negative and two were false positive. Of the remaining lesions, 11 were high grade and 6 were low grade. Mann–Whitney test was applied to compare PET SUV parameters (SUVmax, tumor/grey matter [T/G], tumor/white matter [T/W], tumor/basal ganglia [T/BG], and tumor/cerebellum [T/C]) for these two groups. Furthermore, Spearman correlation coefficients between these parameters and MiB% were obtained. Results: Of all the parameters, SUVmax and T/C ratios were significantly higher for HGG (median SUVmax = 4.52 [range 3.00–7.50]; T/C ratio = 3.00 [range 1.93–4.07]) versus LGG (median SUVmax = 3.46 [range 2.85–3.57]; T/C ratio = 2.34 [range 0.89–2.57]). The respective P values were 0.044 and 0.027. In addition, there was strong correlation between T/C ratio and MiB% (Spearman rho = 0.520; P = 0.039). Conclusion: PET/CT with F18-FDOPA can distinguish between recurrent HGG and LGG. Further, the proliferation index of the tumor cells correlates with the PET semi-quantitative parameters.
| OP21: 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography for response evaluation in head and neck malignancy | | |
Justin Benjamin, Julie Hephzibah, David Mathew, Nylla Shanthly, Regi Oommen
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Background and Objectives: Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck cancers. There has been no established qualitative system of interpretation for therapy response assessment using positron emission tomography-computed tomography (PET-CT) for HNSCC. The study aims to (i) apply Likert scale (Deauville criteria score [DS]) and/or SUVmax to all follow-up PET scans, (ii) determine whether interpretation of follow up PET scans can be improved, (iii) categorize as responders versus nonresponders. Materials and Methods: A retroprospective analysis of nodal status of pre- and post-radiotherapy (RT) PET-CT in patients diagnosed with HNSCC (n = 45) from May 2013 to March 2018 was conducted. Inclusion criteria were Node positive HNSCC, scheduled for organ preservation therapy with curative intent, no initial neck surgery, hypermetabolic neck nodes in pre-RT PET-CT. Follow-up with PET-CT imaging, additional radiological imaging, clinical or histopathological evidence after 6 months was carried out. DS ranged from 1 to 5. Results: Of 45 patients (male/35, female/10, age range 18–80 years [median 54 years]) selected for the study, 37 with DS 1–2 showed no nodal recurrence, 5 with DS 4–5 showed disease progression. Good concordance was noted between DS and clinical response in these patients. Of three patients with DS-3, two showed progression and one was disease free. Number of patients was too small for statistical analysis based on nodal response in DS-3.However, 38/40 patients with DS 1–3 had no nodal recurrence showing a high NPV of 95%. 5/5 patients with DS 4–5 had active disease showing PPV of 100%. Conclusion: Qualitative criteria using DS has been found to be useful in response evaluation of nodal status in HNSCC patients. High NPV (DS 1–3) and PPV (DS 4–5) of follow-up PET-CT in HNSCC is beneficial in restaging of disease and decision-making regarding neck dissection. All patients with a post-RT PET-CT scan DS 4/5 are at great risk of disease progression as they harbor active tumor in the nodes and neck dissection should be considered. Consensus regarding qualitative assessment in future can facilitate PET reporting in clinical practice.
| OP22: 68-Gallium-prostate-specific membrane antigen scan: Is it useful in primary prostate cancer detection?? | | |
Amol Sanjay Menge, Madhuri Shimpi-Mahajan, B. A. Krishna
Lilavati Hospital and Research Centre, Mumbai, Maharashtra, India
Background and Objectives: 68-Gallium prostate-specific membrane antigen (PSMA) scan has proven to be a highly accurate method in the detection of recurrence and metastases of prostate cancer. However, its role in primary lesion detection is yet to be established. Hence, our aim was to assess the role of 68-Ga-PSMA in primary prostate cancer detection. Materials and Methods: We evaluated initial data of our ongoing study on role of PSMA scans in different clinical setting of prostate cancer. Totally, 93 patients have been enrolled in the study so far. There were 12 patients of suspicious prostate cancer either based on elevated prostate-specific antigen (PSA) levels or serial rise in PSA value during monitoring. The patients with positive PSMA scan underwent biopsy. The patients with negative PSMA scan are under observation with PSA monitoring. 68Ga-PSMA-positron emission tomography-computed tomography (PET/CT) was performed as per the standard guidelines. A contrast-enhanced diagnostic CT scan (140 keV, 100–400 mA, dose modulation) was performed for attenuation correction at the time of the PET scan. PSMA uptake were categorized into two types: (a) focal tracer uptake with a cut off of SUVmax 2.5 and (b) heterogeneous uptake with a cut-off of SUVmax 4.0. Results: 9/12 (75%) patients were positive for malignancy on PSMA PET. 4/9 PSMA-positive (44%) patients were negative for malignancy at biopsy suggesting false-positive scans. The PSA range in these patients was 6.8 to 40 ng/mL. All patients with high-grade disease at histology showed PSMA-SUVmax range of 10.74–110.14 and PSA range of 9.4–166 ng.The 3/12 (25%) patients were true negatives. The PSA range in these patients was 7.5 to 9.5ng.The 4/12 (33%) false positives showed SUVmax range 5.6–8.8. Thus, using a cutoff-level for SUVmax of 4, our data showed sensitivity of 100%, specificity of 42%, negative predictive value of 100 %, and positive predictive value of 55.5%. Conclusion: In our initial data, the 68-Ga-PSMA showed low specificity of 42% in the detection of primary prostate cancer lesion. Limitations: This analysis is done in a small number of patients and we will be validating in the larger group in our ongoing study.
| OP23: Prostate-specific membrane antigen receptor expression and metastatic potential in prostate cancer patients | | |
Madhuri Shimpi Mahajan, Amol Sanjay Menge, B. A. Krishna
Department of Nuclear Medicine, Lilavati Hospital, Mumbai, Maharashtra, India
Background and Objectives: Prostate cancer (PCa) patients are risk-stratified on the basis of clinical stage and prostate-specific antigen (PSA) level at diagnosis and the Gleason score (GS) in prostate biopsy. However, these parameters are not completely accurate in discriminating between high- and low-risk diseases, creating a need for a reliable marker to determine aggressiveness. Prostate-specific membrane antigen (PSMA) which are over-expressed in 90% of PCas appear to fulfill this need and these tumor cells are accurately targeted for diagnosis by 68Ga-PSMA-positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) imaging. This study was done to confirm this contention and to find its correlation with metastatic potential. Materials and Methods: This is a retrospective study of total 92 patients which were referred to our department for Ga68-PSMA PET-CT scan. We analyzed data of 38 patients of recently diagnosed biopsy-proven carcinoma prostate. 68Ga-PSMA-PET/CT was performed as per the standard guidelines. Prostatic focalized tracer uptake with a cutoff of standard maximum uptake value (SUVmax) of 2.5 and heterogeneous uptake with a cutoff of SUVmax of 4 was used to discriminate PET positivity from PET negativity as per literature. Depending on the SUVmax in the primary prostatic lesion, patients were divided into two groups, Group 1 with SUVmax <30 and Group 2 with SUV >30 and SUVs were correlated with metastatic spread. Results: 21/29 (72%) patients of Group 1 (29/38) did not show any metastatic spread. 8/29 (27 %) patients of Group 1 showed nodal metastases and 6/29 (20 %) showed skeletal metastases. In Group 2 (9/38), 8/9 (88%) patients showed nodal and 6/9 showed skeletal metastases (66%). Conclusion: In our ongoing study, we found very good correlation between standard maximum uptakes on PSMA scan with differentiation of tumor as seen by the absence of metastatic disease. Our results suggest that with low SUVmax of the primary (<30), possibility of metastatic spread is less likely, and these patients have good prognosis.
| OP24: Utility of fluoro-2-deoxyglucose positron emission tomography-computed tomography in diagnostic evaluation of myeloid sarcoma: A prospective study | | |
Nalli Harish, Rakesh Kumar, Sameer Bakhshi1, Chetan Patel, Ravi Kant Gupta, Anshul Sharma, Akshima Sharma, Chandrasekhar Bal
Departments of Nuclear Medicine and 1Medical Oncology, AIIMS, New Delhi, India
Background and Objectives: Myeloid sarcoma is a rare extramedullary manifestation of acute myeloid leukemia (AML), more common in children than adults. Chloroma is tumor of myeloblasts or immature myeloid cells occurring in an extramedullary site or in bone. It is seen in less than 5% of AML cases. It can herald, follow, or occur with a diagnosis of primary AML by months or can be an initial manifestation of a relapse .Bone marrow biopsy is typically used for diagnosis as well as assessment of treatment, but it cannot identify extramedullary involvement; further, the enhancement pattern on computed tomography (CT) and magnetic resonance imaging (MRI) are quite variable making the diagnosis even more challenging. Therefore, we used fluoro-2-deoxyglucose positron emission tomography-CT (FDG PET/CT) as an imaging modality to evaluate both metabolism and structure and also in identifying the sites of extramedullary involvement while simultaneously evaluating the intramedullary disease. Materials and Methods: A total of 12 AML patients with biopsy proven chloromas were prospectively evaluated with 18F-FDG PET/CT for primary staging. Acquired images were evaluated by two experienced nuclear medicine physicians. All lesions were identified and their SUVmax were calculated using standard protocol. Results: A total of 12 patients (9 males, 3 females), with a mean age 9.09 years (5–19 years) were recruited for the study. On FDG PET/CT, a total of 73 lesions were identified and divided into three groups as masses (n = 26), lymph nodes (n = 20), and soft tissue deposits (n = 27). Eleven patients presented with masses in head and neck region and one presented with a breast nodule. The mean of SUVmax of mass lesions was 5.11 (standard deviation [SD] = 1.66). Ten patients had soft tissue deposits which included pleura, spleen, muscle, skeletal sites, prevertebral and intraspinal deposits (mean SUVmax = 4.21; SD = 2.35). Conclusion: 18 FDG PET/CT is an excellent diagnostic modality for staging of chloromas and its disease extent. It has proved its usefulness in detecting unknown extramedullary lesions.
| OP25: Incidence and distribution of extramedullary disease in patients with multiple myeloma as detected on 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography: A single-center longitudinal study of 124 patients | | |
Braj Kishore Singh, Kartikey P. Solanki
Department of Nuclear Medicine, Army Hospital, R and R, New Delhi, India
Background and Objectives: Multiple myeloma (MM) is a malignant plasma cell proliferative disorder typically contained within the bone marrow (medullary disease). Infrequently, extramedullary disease (EMD) occurs with the presence of malignant plasma cells outside of the bone marrow within soft tissue, lymph nodes, muscle, skin and other organs (extramedullary myeloma). EMD is more often seen with relapsed refractory disease and may be associated with decreased overall survival. The aim of this study was to determine the incidence EMD in MM and sites of its extramedullary dissemination. Materials and Methods: A total of124 diagnosed cases of MM at our institution underwent fluoro-2-deoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) imaging. For each PET scan, each patient was intravenously administered 8–10 mCi (370–555 MBq) of FDG with imaging at 60 min postinjection extending from the top of the head to the soles of the feet. EMD identified on PET was confirmed by biopsy or clinical follow-up. The laboratory values most frequently elevated and associated with EMD were examined. A strict definition of EMD was followed which required that to be called EMD, the lesion must not have risen from any bone. Thus, masses arising from the bone with a soft tissue component were not considered extramedullary. Results: Of 124 patients studied, 22 patients (17.7%) had EMD. In 6 of the 22 patients, EMD was present at time of diagnosis of MM. The EMD sites involved included the temporal area (not arising from the skull) soft tissue, muscle, chest wall not attached to bone, abdominal/pelvic masses, kidney, sinus, paraspinal, subcutaneous tissue, and mediastinum. The median number of extramedullary sites per patient was 1. Conclusions: The incidence of EMD has increased, probably due to the availability of more sensitive imaging techniques and the prolongation of patients' survival. A whole-body approach of FDG-PET/CT offered the advantage of detecting sites/presence of EMD which was not included in the field-of-view on other imaging modalities.
| PP11: Role of fluoro-2-deoxyglucose positron emission tomography-computed tomography in assessing response to targeted therapy in metastatic lung cancers | | |
Sreya Ghosh, Nilendu Purandare, Ameya Puranik, Sneha Shah, Archi Agrawal, Venkatesh Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
Background and Objectives: Receptor-specific therapies are indicated in metastatic lung cancers. Metabolic response assessment of targeted therapy is better than assessing the size. This study is a retrospective analysis, where we compared morphologic and metabolic response of computed tomography (CT) and positron emission tomography (PET). Materials and Methods: Thirty-one patients (23 males, 8 females with an age range of 42–77 years) with epidermal growth factor receptor (EGFR)-positive metastatic lung cancer on gefitinib, who underwent PET/CT, at baseline and at 4–6 weeks, were assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and European Organization for Research and Treatment of Cancer (EORTC) criteria. Results: Concordance between RECIST 1.1 and EORTC was seen in 26 (83.7%) patients. Discordance was seen in 5 (16.3%) patients. In patients with discordance, the results were confirmed by follow-up imaging. Metabolic EORTC criteria changed the disease status from stable disease to partial response (3 out of 5) and progressive disease (2 out of 5) in these five patients. Conclusions: Metabolic criteria using PET/CT could accurately predict response as well as disease progression early in the course of targeted therapy, compared to morphologic criteria. In addition, early metabolic response assessment can predict refractoriness of therapy.
| PP12: 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography scan findings in anaplastic lymphoma kinase-positive carcinoma lung: Institutional experience | | |
Naveen Kumar Reddy Akepati
Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Background and Objectives: Lung cancer is the most common cancer worldwide and leading cause of cancer mortality. Recently, many targeted therapies such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) mutations are being used with gratifying results. Our objective was to evaluate findings in ALK-positive carcinoma lung in staging 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18FDG PET/CT) scan. Materials and Methods: Among patients referred for staging PET/CT scans between 2015 and 2017, 400 of them underwent ALK mutation testing. 18 patients were ALK positive. Images are reviewed; SUVmax value and CT finding of primary mass, regional nodal status, and distant metastases are evaluated and analyzed. Results: Primary mass was centrally located in 17 cases (94.4%), solid in nature in all cases, smooth and lobulated margins in 13 cases (72.2%), pleural retraction in three cases (15.8%), and airbronchograms in one case (5.3%). Median size of the mass was 2.95 cm (interquartile range 2.59–4.18). Median SUVmax value was 12.85 (interquartile range 11.00–15.2). Fifteen cases (83.3%) had distant nodes, one case had only ipsilateral hilar nodes, one case had ipsilateral hilar and mediastinal nodes, and one case had bilateral hilar and mediastinal nodes. Most of the cases had perinodal spread. All cases have distant metastases. Distant spread includes lung metastases (seven cases), lymphangitis carcinomatosis of lung (two cases), liver (seven cases), adrenals (five cases), bones (six cases), pleura (two cases), brain (one case), soft tissue (one case), and distant lymph nodes. Conclusion: Characteristic features of ALK-positive carcinoma lung in staging 18FDG PET/CT scan include centrally located solid mass with smooth and lobulated margin, median size of 2.95 cm, and median SUVmax value of 12.85. Majority of the tumors had distant nodes, and all had distant metastases.
| PP14: Feasibility of combined visual and semi-quantitative response assessment-based reporting for fluoro-2-deoxyglucose avid lymphomas | | |
Abhishek Khare
Platinum Imaging Centre, New Delhi, India
Background and Objectives: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT scans)-based interim (IPET) and end of treatment response assessment (EOT PET) scans are currently the modality of choice for FDG avid lymphomas. Before 2009, both visual and semi-quantitative measurements were being used for response assessment of FDG avid lymphomas. However, previously developed visual response assessment criteria such as international harmonization criteria (IHP 2007) did not gain widespread acceptance due to the high rate of false-positive results while semi-quantitative measurements in form of maximum standardized uptake value (SUVmax) lacked consistency due to dependence on biological, technical, and scanner factors. In an effort to standardize response assessment, a new visual response criterion was formulated in 2009 and came to be known as Deauville's criteria (DC). While DC has been universally accepted for response assessment, there are issues of observer bias, intermediate zone (score 3), and lack of objective assessment using DC. Authors here have compared combined visual and semi-quantitative parameters for response assessment and explore the feasibility of whether both can be incorporated in reporting. Materials and Methods: The study included 86 patients of proven baseline FDG avid lymphomas and who underwent serial IPET and EOT PET scans in the same PET scanner with similar imaging parameters in a single institute study. Visual assessment was based on DC and semi-quantitative on SUVmax body weight (SUVmax bw). The visual assessment was compared with the mean of SUVmax (mean SUVmax) by averaging lesions for various response categories such as complete metabolic response (CMR), partial metabolic response (PMR), stable disease (SD), and progressive disease (PD) based on PET response criteria in solid tumors at IPET and EOT PET scans. Spearman rank correlation coefficient was computed to test the association between DC and mean SUVmax. Data analysis was done using Statistical Package for Social Sciences version 16.0. All “P” < 0.05 were considered as statistically significant. Results and Conclusion: Combining visual assessment with mean SUVmax comparison in various response categories had significant Spearman's rho correlation coefficient at IPET (0.782) and EOT PET (0.837). Combined reporting with both visual and semi-quantitative results is feasible and recommended if done in the same PET scanner with similar imaging parameters. This method obviates interobserver bias and provides objectivity to visual analysis, making it more robust for clinicians to accept the results and modify/intervene or continue the treatment plan.
| PP15: Quantification of 68Ga-DOTATATE uptake with time in normal organs and blood pool: An exploratory analysis with implications for quantification ratios | | |
Ashwini Kalshetty, Biju Menon, Sharmila Banerjee, Sandip Basu
Radiation Medicine Centre, Mumbai, Maharashtra, India
Background and Objectives: Physiological uptake of 68Ga-DOTATATE is observed in the liver, spleen, salivary glands, pituitary, bowel, and urinary tract. Although there is a standard protocol for somatostatin receptor imaging with 68Ga-based somatostatin analogs, there is a relative paucity of data regarding the quantification of physiological uptake in these organs, which is important for calculation of quantification ratios (particularly when there is variation in the time of acquisition of the study). Materials and Methods: A retrospective analysis of 44 patients of neuroendocrine tumors and medullary carcinoma of thyroid who had undergone 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT) imaging for staging and without any hepatic or splenic metastases was undertaken. The mean SUV was calculated based upon 3D-region of interest (ROI) at 3 distance/location points and with fixed diameter of 3 cm and 40% threshold-based automatic segmentation. These ROIs were recorded in liver, spleen and kidneys. Similarly, a 2-location point mean SUV was recorded for blood pool in aorta and the pituitary gland. In all patients, the injected dose, time of injection, waiting duration, time of acquisition, and patient BMI were also recorded. The cases were also categorized into three depending on the time of acquisition: up to 80 min, 81–130 min, and >130 min. Mean and standard deviation for SUVs were calculated for each organ and duration category. A multivariate regression analysis of injected dose, duration of waiting, and mean SUV were plotted for relationship between the variables. ANOVA analysis was performed for testing the significance between these three groups of duration categories. Results: The respective mean SUVs in various organs in three categories of acquisition of study, viz., 80 min, 81–130 min, and >130 min were as follows: 8.46, 11.2, 28.05 in liver; 19.75, 27.3, 46.53 in spleen; 24.09, 16.59, 32.96 in kidneys; 6.67, 5.77, 7.78 in pituitary; and 3.74, 4.73, 12.27 in blood pool. ANOVA analysis resulted in P <0.001 when mean SUVs were compared with waiting duration. Conclusion: There was a general trend seen that physiological SUVmean increases with time in somatostatin receptor-based PET. Hence, in high-volume centers where strict adherence to protocol is difficult, this variation may need to be considered especially in the cases where quantification ratios (e.g., lesion to liver/lesion to spleen) are undertaken as parameters of treatment response in 68Ga-DOTATATE PET-CT.
| PP16: Comparative study on intraoperative localization of sentinel lymph node in breast cancer patients using Tc-99m sulfur colloid and blue dye | | |
Vindhya Malasani
Fortis Memorial Research Institute, Gurgaon, Haryana, India
Background and Objectives: A sentinel lymph node (SLN) is considered to be the first lymph node which is draining the tumor site. Radioactive Tc-99m-labeled sulfur colloid and vital blue dye such as isosulfan blue or methylene blue or the combination of the both are generally used for sentinel lymph node localization. In this study, we compare the sensitivity of both the methods to establish an effective method for SLN localization among early cases of breast cancer. Methods and Results: Forty incidental cases consulting the hospital between 2015 and 2017 and diagnosed with early breast cancer (Stage T1N0M0 and T2N0M0) were subjected to SLN involvement and detection by both radiocolloid and dye. 99mTc-labeled filtered sulfur colloid was administered intradermally in the periaerolar region in the tumor quadrant, 30 min–1 h before the surgery. 1 ml methylene blue dye was administered, intraparenchymally, in circumareolar region during the surgery. All radioactive lymph nodes were removed until background activity is less than one-tenth the ex vivo value of hottest node. All the blue dye positive nodes whether or not radiocolloid positive were excised and labeled accordingly and sent for histopathological examination. Results: SLN detection and localization was positive in 36 patients with radiocolloid and 34 patients with blue dye and in two patients neither of these showed any signs of involvement. The ability to identify the SLN for colloid alone, blue dye alone, and the combination of both the methods was 90%, 85%, and 95%, respectively. The concordance between blue dye and radiocolloid was 80%. Metastatic lymph node involvement was found in 13/38 (34.2 %) of patients. Conclusion: Both the radiocolloid and dye drain to the same SLN node; however, the SLN detection ability was found to be high when both the methods are used in combination.
| PP17: Prognostification in brain hypometabolism and concurrent high tumor metabolism in cancer patients at initial staging observed on 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography scan | | |
H. J. Prathap, Shwetal Pawar, Roshni Bhandary, Suruchi Shetye
Department of Nuclear medicine, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
Background and Objectives: Reduced brain metabolism in the absence of cognitive impairment with concurrent high-grade metabolic activity in primary tumors of cancer patients are sometimes observed on fluoro-2-deoxyglucose positron emission tomography (FDG-PET); and it is associated with high-risk disease, lower complete response rate to chemotherapy, and potentially shorter progressive-free survival in lymphoma. The purpose of the study was to assess the prognostic role of 18F-labeled fluoro-2-deoxyglucose (F-18 FDG) uptake in brain in comparison to the primary tumor in various malignancies at staging. The study aims to investigate the prognostic value of decreased brain metabolism in patients with concurrent high-grade metabolism in tumors at primary staging. Materials and Methods: This study is conducted in 22 biopsy-proven cancer patients referred for staging of the disease. Inclusion criterion was visually reduced brain uptake than the primary tumor on F-18 FDG PET study done for primary staging. Patients with brain metastases were ruled out. The causes for decreased brain uptake such as hyperglycemia, anemia, and dementia were excluded. 18F-FDG (mean dose 5.4 mCi) was injected, at 60 min post-18F-FDG injection PET/CT (vertex to mid-thigh) scan were done. Two PET variables, the maximum standardized uptake values (SUVmax) and average SUV (SUVmean) of primary tumor and brain, were measured. Patients were assessed for cognitive function using MMSE and performance using Karnofsky score. The patients were followed up to look for overall survival. Patient characteristics were compared using Fisher's exact test. Survival analyses were performed using Kaplan–Meier curves and compared using log-rank test. Results: We included 22 patients in the study. 13 (59%) patients had brain hypometabolism with SUVmax <7 by initial PET scan. The brain hypometabolism patient had a median age of 55 years (range, 32–90 years) and 32 % males. Six (46%) patients out of 13 patients with brain hypometabolism survived for a maximum duration of 2 months and the other 7 patients are on palliation. Mean tumor:brain uptake is 2.38 (range 1.1–5.8).The mean of brain SUVmean is 4.5 (range 1.34–10.35). Patients with brain hypometabolism seemed to have a shorter overall survival compared to those with normal brain metabolism. Conclusion: In our study, the brain hypometabolism was a phenomenon observed among many newly diagnosed cancer patients. It is associated with higher risk disease and potentially shorter overall survival. Further studies in larger patient population are needed to determine the true prognostic significance.
| PP18: Incremental value of Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography for preoperative risk stratification of prostate cancer | | |
U. N. Pallavi, Ishita B. Sen, Sanjay Gogoi, Vindhya Malasani, Parul Thakral, Vineet Pant
Fortis Memorial Research Institute, Gurgaon, Haryana, India
Background and Objectives: Prostate cancer (PC) is the second most common cause of cancer. PC burden is growing worldwide and the most crucial part of patient management is precise local staging of disease. Galluim-68 prostate-specific membrane antigen positron emission tomography-computed tomography (68Ga PSMA PET/CT) scan help in accurate staging of PC owing to its high PSMA avidity and specificity. The aim of this prospective observational study was to determine the accuracy of 68Ga PSMA PET CT in locoregional staging of intermediate- and high-risk PC using histopathology from radical prostatectomy specimens as a gold standard. Materials and Methods: Twenty-six patients with biopsy-proven prostate carcinoma were enrolled in this study. Whole-body 68Ga PSMA PET/CT scans were performed at baseline. The imaging findings were compared to the prostatectomy histopathology. These findings were also compared with multiparametric magnetic resonance imaging (mpMRI). Results: On follow-up, 22 patients underwent radical prostatectomy, one patient underwent radiation therapy, and three did not undergo surgery owing to skeletal metastases. In 22 patients, who underwent prostatectomy, a total of 58 lesions in prostate and extra-prostatic region were identified and confirmed by histopathology. The categorization of lesions were as follows: 42 lesions in prostate gland, seven in extraprostatic region, five in lymph nodes, three in seminal vesicle, and one in bladder neck. Of these 58 lesions, PSMA PET/CT detected a total of 49 lesions and mpMRI detected 32 lesions. Of the nine lesions for which PSMA PET/CT showed false-negative results, five were in prostate gland, two in seminal vesicles, and two in pelvic lymph nodes (size <1.0 cm). PSMA PET/CT showed better sensitivity for locoregional staging than mpMRI (84.5% vs. 55.0%) with discordance seen in 15 lesions (32.6%) between the two diagnostic modalities mainly in extra-prostatic region (46.6 %). The specificity was 100% and 98% for PSMA PET/CT and MRI, respectively. Conclusion: 68Ga-PSMA PET CT provided superior detection of locoregional preoperative staging of PC as compared to mpMRI in intermediate- and high-risk PC patients.
| PP19: Chemokine 4 receptors overexpression imaging in lymphoma patients using Ga-68-labeled CPCR4 trifloroacetate | | |
Rakhee Vatsa, Jaya Shukla, Shashank S. Singh, Nivedita Rana, Bhagwant Rai Mittal
Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India
Background and Objectives: Chemokine receptors (CXCRs) have demonstrated their vital role in various pathologies including inflammation, neoplasia, and metastases. Overexpression of CXCR4 has been known as an adverse prognostic factor in various malignancies such as leukemia, multiple myeloma, breast, lung, and gliomas. In the present study, the role of Ga-68 CPCR4-trifloroacetate (synthetic analog of natural ligand SDF-1α) as a noninvasive imaging tool of CXCR4 was evaluated in lymphoma patients. Materials and Methods: Ga-68 was used to label commercially available CPCR4-trifloroacetate in-house in semi-automated fluidic module. Peptide (20 μg) was incubated at 4.0 pH with Ga-68 (20–25 mCi) for 10 min at 95°C. Purification of the final product was done by C-18 cartridge. Quality control was performed to ensure the use for intravenous administration. The lymphoma patients (n = 5) were recruited. To determine the maximum uptake of radiotracer, serial PET images were acquired from base of skull to mid-thigh at 1 and 8 min (30 s/frame) min, 15 min and 30 min (45 s/frame), 60 min (90 s/frame), 120 min (120 s/frame), and 180 min (180 s/frame) postinjection of 4 mCi of Ga-68 CPCR4-trifloroacetate. The images at 60, 120, and 180 min were acquired postvoid. All computed tomographic (CT) images were acquired at 10 mA current. A lesion was judged positive if nonphysiological tracer uptake was seen. Maximum standardized uptake value (SUVmax) was measured by drawing 1 cm 3 region of interest over mediastinal blood pool, liver, spleen, bone marrow, and the lesions. Results: Radiolabeling yield of >95% with >99% radiochemical purity was achieved. Imaging was performed in patient (2 males and 3 females, age range 39–70 years) diagnosed with B-cell NHL with no extranodal involvement. Radiotracer was observed to be cleared rapidly from the mediastinal blood pool within 15 min. The average SUVmax values were 3 (1 min), 3.8 (8 min), 2.1 (15 min), 3.1 (30 min), 4.8 (60 min), 4.9 (120 min), 6.9 (180 min) in serial images. As evident, the SUVmax in pathological lymph nodes was increased in delayed images. Physiological uptake of radiotracer was seen in liver, spleen, and bone marrow which showed a decreasing trend of SUVmax over time. The tracer was found to be excreted primarily through kidneys. Conclusion: CPCR4-trifloroacetatewas successfully radiolabeled with Ga-68 for patient's selection and response assessment to novel anti-CXCR4 therapy. Delayed imaging at 3 h are preferred for attaining good tumor to background ratio.
| PP20: Role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in clinically suspected paraneoplastic neurological syndrome | | |
Arun Ravi John, A. G. Pandit, Braj Kishore, Anurag Jain, M. G. Vishnoi
Department of Nuclear Medicine, Army Hospital (R and R), New Delhi, India
Background and Objectives: Paraneoplastic neurological syndrome (PNS) describes a spectrum of rare, heterogeneous neurological conditions associated with an underlying malignancy. PNS may involve both central nervous system and peripheral nervous system comprising several diseases such as paraneoplastic sensorimotor polyneuropathy, paraneoplastic cerebellar degeneration, limbic encephalitis, paraneoplastic encephalomyelitis, brainstem encephalitis, opsomyoclonus syndrome, in addition to other less frequently occurring entities. Clinical diagnosis of PNS is difficult, with frequent misdiagnosis. The literature suggests an underlying immune-mediated pathophysiology. With direct tumor therapy being the most effective method of stabilizing patients, there is a strong emphasis on detecting underlying tumors. The sensitivity of conventional computed tomographic (CT) imaging is often inadequate in such patients. We conducted a retrospective study to study the utility of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-CT (18F FDG-PET/CT) in clinically suspected PNS. Materials and Methods: We identified 30 patients who underwent 18F FDG PET-CT for clinically suspected PNS at our hospital between January 2014 and July 2018 and compared the results to conventional investigation that is a contrast CT scan. Results: Seven patients had FDG-PET/CT tracer avidity suspicious of malignant disease, and six of these were subsequently diagnosed with cancer. No patient who was PET negative was detected with a malignancy. Sensitivity and specificity were calculated to be 100% and 95.8%, respectively, with positive predictive value of 85% and negative predictive value of 100%. This compares to a sensitivity and specificity of 50% and 95%, respectively, for a contrast CT scan. Conclusion: The findings of the study are commensurate with the previous studies and support the diagnostic accuracy of 18F FDG-PET/CT for the detection of underlying malignancy if any in suspected PNS.
| PP21: The role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in patients with primary of unknown origin | | |
T. M. Ginsha, H. K. Mohan, B. Harish B, B. S. Srinath, R. Anjan Bharathi, Thippeswami, S. Patil
Sri Shankara Cancer Hospital and Research Centre, Bengaluru, Karnataka, India
Background and Objectives: Patients being assessed for identifying primary site of disease are referred to undergo 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F FDG PET/CT) study. 18F FDG PET/CT is widely used for diagnosis and staging of most cancers as it helps in early and accurate imaging. In this study, we aim to assess the usefulness of 18F FDG PET/CT for the diagnosis of primary in patients referred to Department of Nuclear Medicine. Materials and Methods: Ninety consecutive patients (female = 38, male = 52, median age = 63.4 years) referred to the Department of Nuclear Medicine for a PET/CT study between November 2017 and August 2018, in whom conventional diagnostic work-up failed to identify the primary site of disease, were included in the study. Eighty-five patients had a definite site of metastatic disease while five patients were assessed for possible paraneoplastic syndrome. Results: Of the 90 patients, F18 FDG PET-CT was able to clearly identify a site of primary in 59/90 patients (65.5%) and failed to identify in 20 patients (22.2%). In 11 patients (12.2%), it could guide clinician toward a possible site if disease and biopsy. The most common metastatic sites were lymph nodes, bone, and liver. 40% presented with lymphadenopathy and 18% with bone metastasis. 4.5% patients presented with multiple metastasis. Lung carcinoma was the most common single site of primary (n = 13) closely followed by head and neck (n = 12). Gastrointestinal and hepatobiliary system together accounted for 32.75% (n = 19). Final confirmatory biopsy was available in 44 patients. Rest were either dead/palliative/outpatient patients/lost to follow-up. Of the 44 patients, PET-CT correctly identified site of primary in 80% (n = 35) and suggestive of the primary site in four cases (9%). PET-CT was incorrect in 1/44 cases (2.2%) and unable to identify site of primary in four cases (9%). Conclusion: 18F FDG PET/CT correctly identified or was helpful in directing the clinician toward the right site to biopsy in 78% of cases. 18F FDG PET/CT study plays a crucial role in the evaluation of patients with unknown primary.
| PP22: Role of metabolic parameters on baseline 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in prognostication of locally advanced breast cancer | | |
N. Zaeba, Sneha Shah, Nilendu Purandare, Archi Agrawal, Ameya Puranik, Venkatesh Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Centre, Mumbai, Maharashtra, India
Background and Objectives: To evaluate role of metabolic parameters on baseline fluoro-2-deoxyglucose positron emission tomography-computed tomography (FDG PET/CT) in prognostication of patients with locally advanced breast cancer. Materials and Methods: This was a retrospective observational study. Female patients with biopsy-proven locally advanced breast cancer who were referred to our department for baseline FDG PET/CT scan during the period from January 2011 to June 2015 and whose follow-up was available for minimum of 3 years were included in the study. Patients were segregated into metastatic and nonmetastatic. Patients with metastases were excluded from the study. Recurrence was confirmed clinical/radiological follow-up. Suitable cut-off points for SUVmax, SUVmean, MTV, and TLG were obtained using receiver operating characteristic curve and survival curves for disease-free survival (DFS) were constructed by using the Kaplan–Meier method. Results: A total of 150 patients were referred for baseline FDG PET/CT. A total of 43 patients with metastases and 30 patients whose follow-up was not available were excluded from the study. A total of 77 patients were included in the study. Twenty-two patients developed recurrence. Median DFS was 68 months. There was statistically significant difference in DFS using mean target volume (MTV) mean cutoff 26.8 (74 months vs. 49 months) (P = 0.007). Difference in DFS for SUVmax, SUVmean, TLG of primary tumor, and whole body MTV did not show any statistically significant correlation. Conclusion: MTV mean values were significant predictors of DFS in locally advanced breast cancer. Rest of the metabolic parameters showed definitive trend toward predicting DFS, although statistically significant results could not be obtained due to small sample size.
| PP23: “To do or not to do” presurgical positron emission tomography-computed tomography in patients with oral squamous cell carcinoma | | |
S. Manjunath, H. K. Mohan, T. M. Ginsha, B. S. Srinath, Vinay Singh Yadav, S. Girish Rao, Sudha
Sri Shankara Cancer Hospital and Research Centre, Bengaluru, Karnataka, India
Background and Objectives: 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) has been utilized in the evaluation of several different cancer types including head and neck cancer. However, data on the accuracy of FDG-PET/CT in comparison to histopathology have been preliminary to date. We present our experience with FDG-PET/CT in the staging of oral squamous cell carcinoma (SCC), with comparison to clinical assessment and the definitive gold standard of surgical histopathology. The study aims to prospectively evaluate the use of FDG-PET/CT in the initial staging of oral SCC. Materials and Methods: Nineteen consecutive patients diagnosed with oral SCC who were referred to undergo PET/CT staging were included in the study. Clinical staging was done by a senior maxillofacial surgeon while PET/CT was evaluated by a senior nuclear medicine physician and a radiologist. 10/19 were male. Clinical staging and PET/CT staging of the tumor were then compared with the postsurgical histopathology. Results: Postsurgical histopathology was available in 13 patients. Four patients did not undergo surgery due to diagnosis of M1 disease on PET/CT, while two refused surgery. Clinical staging suggested Stage 3 disease in nine patients and stage 4 in 10 patients. None of the patients were Stage 1 or Stage 2. PET/CT suggested Stage 1 in 1 patient, Stage 3 in 4 and Stage 4 in 14 patients. In 4/19 (22%), PET/CT diagnosed M1 who had confirmation with biopsy. PET/CT upstaged the disease in seven patients and downstaged in one when compared to the final histopathology among which eight were T-stage upstaging and 6 were nodal upstaging. One patient demonstrated nodal downstaging. Clinical examination staging upstaged in six and downstaged in two patients among which two were T-stage upstaging and six nodal upstaging. It downstaged 2 T-stage and 1 nodal status. PET/CT when compared to Clinical staging showed T-stage upstaging in three and nodal upstaging in six patients. It was found to downstage T-stage in 2 and nodal status in 1 patient. Furthermore, PET/CT identified M1 stage in 4 patients which was confirmed on biopsy. Conclusion: We noticed a trend of upstaging in PET/CT compared to the final histopathological staging. This is likely due to local inflammatory changes and infections accompanying the lesions. PET/CT identified M1 disease in patients with higher stage disease, resulting in change of management. PET/CT is a valuable clinical tool in presurgical staging of advanced clinically staged oral SCC.
| PP24: Detection rates and superiority of gallium-68-prostate specific membrane antigen positron emission tomography/computed tomography in castration-resistant prostate cancer: Benefits in decision-making in specific clinical situations | | |
David Mathew, Regi Oommen, Julie Hephzibah, Nylla Shanthly
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Background and Objectives: To evaluate the utility of gallium-68-prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) in resolving specific clinical dilemmas in castration-resistant prostate cancer (CRPC). Methods: Analysis of 68Ga-PSMA PET images performed during June 2016 and August 2018 in our department in patients with CRPC to assess the detection efficiency of metastases in bones and soft tissues and its superiority over CT in determining the activity of disease. Results: Study group: 26 men with CRPC (age 47–85 years, mean 68.4 years). Lesions in prostate = PET-positive – 22 patients. CT-positive – 15 (7 did not reveal). Active versus remission = CT could not differentiate in 14 patients. Bone metastases = PET – 7 had active bone metastases in PET images, CT – 7 false positive in 7 (all sclerotic). Node metastases = PET 8 had active disease and CT – 9 false positive. Conclusion: In CRPC, 68Ga-PSMA PET/CT was beneficial in answering specific clinical questions like such as activity in metastases in bone and soft tissues and the primary site.
| PP25: Evaluation and comparison of semi-quantitative response assessment parameters on 68Ga-DOTATATE positron emission tomography-computed tomography in patients undergoing PRRT for neuroendocrine tumors | | |
Ashwini Kalshetty, Biju Menon, Sharmila Banerjee, Sandip Basu
Radiation Medicine Centre, Mumbai, Maharashtra, India
Background and Objectives: PRRT is an important targeted therapeutic modality for patients with progressive/uncontrolled functional symptoms from metastatic neuroendocrine tumors (NETs). The RECIST 1.1 or PERCIST criteria has not been well standardized for response assessment in patients undergoing PRRT, given the variable results on different studies, variation of dose injected, and time of acquisition of PET-CT studies, especially in a high-volume center. Hence, we tried to look at different quantitative PET parameters in assessing the response. Materials and Methods: In this study, we analyzed 27 patients of histopathologically proven NETs who had undergone 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT) imaging at baseline and after 3–4 cycles of PRRT. Automated tumor segmentation with regions of interest ROI of 40% SUV threshold in tumor and a 3D ROI with fixed diameter of 3 cm at 3 location points in liver, spleen, and blood pool were recorded. SUVmax of overall 37 lesions with meanSUV in nonspecific areas (liver, spleen, and blood pool) were analyzed. Injected dose, time of injection, waiting duration, time of acquisition, and patient BMI were also noted. Study Analysis: An expert classified the patients into three response categories based on overall clinical profile (including imaging, biochemical markers, and patient symptomatology) as stable disease, partial response, and progressive disease. Difference between pre- and post-therapy SUVmax (ΔSUVmax), tumor to nonspecific uptake (ΔT/NSU), and tumor to spleen (ΔT/S) was calculated. Lesion-wise comparison between all three parameters was performed for relation between the variables by using Pearson's correlation test. One-way ANOVA analysis was performed for parameter-wise comparison across all three response categories. Results: There was no significant relation between ΔSUVmax and ΔT/NSU or ΔT/S ratios on Pearson's correlation test (P = 0.2 for ΔT/NSU and P = 0.3 for ΔT/S). None of the above three parameters demonstrated any significant difference in any of the response categories as well (P = 0.7 for ΔSUVmax, P = 0.2 for ΔT/NSU, and P = 0.07 for ΔT/S). Conclusion: ΔSUVmax, ΔT/NSB, or ΔT/S ratios did not correlate for response assessment in targeted therapies. They did not show any statistically significant difference to distinguish any of the response category. Hence, there is a necessity to continue efforts for quantification of response in such cases. Further prospective studies may help in clarifying the role quantitative parameters.
| PP26: Ga-68 DOTATATE positron emission tomography-computed tomography imaging in tumor-induced osteomalacia | | |
Julie Hephzibah, David Mathew, Nylla Shanthly
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Background and Objective: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures, and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23). Lesions are typically small; benign mesenchymal tumors found in bone or soft tissue. Locating the tumor is critical as complete removal is curative. If it is not localized, or surgical resection is not possible, medical therapy with phosphate and active Vitamin D is usually successful in healing osteomalacia and reducing symptoms. The study aims to evaluate the utility of Ga68 DOTATATE positron emission tomography-computed tomography (PET-CT) imaging to localize cause for TIO. Materials and Methods: Retrospective analysis between March 2015 to March 2018 of patients who presented with nonspecific generalized/localized unexplained bone pains and proximal myopathy with hypophosphatemia and who underwent Ga68 DOTATATE PET-CT imaging was conducted. Biochemical parameters estimated at baseline were serum phosphate (S.P), serum calcium (S.Ca), parathyroid hormones (PTH), serum alkaline phosphatase (SAP), FGF23 (C-terminal), 24 h urine phosphorous, Vitamin D levels, and tubular maximum for phosphate corrected for glomerular filtration rate (TMPGFR mmol/L), bone scan when applicable. Results: A total of 27 patients with suspected TIO, aged between 18 and 65 years, 18 males and 9 females, were studied. A total of 19 (70.3%) patients found to be positive for a possible mesenchymal tumor were included. Most common site of tumor was lower limb (73%). Most common presenting symptom was bone pain (80%) followed by muscle weakness (13.3%). Mean biochemical parameters were FGF23: 448.0 RU/mL, which included two patients with normal FGF23 value at baseline, S.P: 1.4 mg%, serum calcium: 8.9 mg%, SAP: 293.6 U/l, serum 25-hydroxyvitamin D: 30.8, and PTH: 100.8 pg/ml. TMPGFR was calculated in 13 patients and was found to be 1.01 mmol/L. Overall, nine patients underwent surgery, all of whose biopsy was reported as phosphaturic mesenchymal tumor. During 3-month follow-up, only one patient had 68Ga-DOTATATE PET/CT which showed no evidence of any residual lesion/new lesions. Following surgery, S.P measured in all nine patients had normalized and serum FGF23 levels measured in 7/9 patients returned to normal levels in 1 week to 4 months. Conclusion: In patients presenting with musculoskeletal pain and severe weakness, TIO should be considered as a possible cause. Although localization of these small mesenchymal tumors are challenging, it should be extensively investigated and excised as clinical and biochemical changes are possibly reversible. Ga68-DOTATATE PET/CT is useful imaging modality for localizing cause for TIO.
| PP27: Role of 68Ga-prostate-specific membrane antigen positron emission tomography-computed tomography in the evaluation of primary prostate cancer and histopathological correlation | | |
Akshay Kumar, Harsh Mahajan1, Promila Pankaj2, Ritu Verma1, Ajay Sharma1, Ethel S. Belho1
SGPGIMS, Lucknow, Uttar Pradesh, 1Sir Ganga Ram Hospital, 2Max super Specialty Hospital, New Delhi, India
Background and Objectives: Adenocarcinoma of prostate is the second most common cause of cancer death among men. Prostate-specific membrane antigen (PSMA) represents a cell surface target suitable for imaging metastatic lesions as it is expressed by nearly all prostate cancer cells with enhanced expression levels in poorly differentiated, metastatic, and hormone-refractory carcinomas. The study aims to evaluate role of 68Ga-PSMA positron emission tomography-computed tomography (PET/CT) in the evaluation of primary prostate cancer and its histopathological correlation. Materials and Methods: A total of 150 patients with recently diagnosed/suspected primary prostate cancer, who underwent 68Ga-PSMA PET/CT scan, were evaluated. Semi quantitative PET parameter (SUVmax) of the evident prostatic lesion on 68Ga-PSMA PET/CT scan was measured. Histopathological analysis of biopsy specimen was considered as reference standard. Results: The sensitivity, specificity, PPV, NPV, and accuracy of 68Ga-PSMA PET/CT for the detection of primary prostate cancer were 90.3%, 80.7%, 95.7%, 63.63%, and 88.66%, respectively. The mean SUVmax of primary lesion in biopsy-proven cases was 15.45 ± 15.66, which was significantly higher than the mean SUVmax obtained in biopsy-negative cases which was 6.06 ± 9.25. However, the study failed to find any significant correlation between SUVmax of the primary lesion and Gleason's score (r = 0.371) and PSA levels (r = 0.613). Ga-68 PSMA scan identified additional nodal, bony, and visceral metastases in 52 cases. Conclusion: 68Ga-PSMA PET/CT scan is a sensitive modality for the evaluation of primary prostate cancer, correlating well with histopathology. It is a sensitive modality for finding additional sites of metastases, thereby guiding their overall clinical management, and can be included in the diagnostic algorithm of prostate cancer patients before starting the optimal treatment. In addition, 68Ga-PSMA PET/CT also assists in guiding biopsies for histopathologic evaluation for the diagnosis of prostate cancer.
| PP28: 18F-flourodeoxyglucose positron emission tomography-computed tomography in initially treated cases of ovarian cancer presenting with biochemical relapse in follow-up | | |
Shelvin Kumar Vadi, Rajender Kumar, Bhagwant Rai Mittal, Anwin Joseph Kanaval, Anish Bhattacharya, Vinita Jain1
Departments of Nuclear Medicine and 1Obstetrics and Gynecology, PGIMER, Chandigarh, India
Background and Objectives: The study aims at evaluating the diagnostic utility of 18F-flourodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) in patients of ovarian cancer presenting with biochemical recurrence after initial standard therapy for the primary disease. Materials and Methods: Retrospective evaluation of FDG PET/CT data of 39 female patients with pathologically proven adenocarcinoma ovary was done. Patients who had initial standard treatments, referred for posttreatment surveillance for detection of biochemical relapse (either one value of CA 125 >30 IU/ml or two consecutive increases in values) fulfilled the inclusion criteria. Clinical-radiologic follow-up/response to chemotherapy was taken as reference standard. Follow-up was possible only in 18 patients (mean follow-up period of 45.8 months). Results: Thirty-nine female patients (mean age: 52.5 years, range: 26–68) with histopathologically proven adenocarcinoma of ovary, who underwent initial standard treatments therapy with surgery (hysterectomy and bilateral salpingoopherectomy) followed by chemotherapy for the primary disease, underwent 18F-FDG PET/CT when they were detected with biochemical relapse in the follow-up. The mean time interval between the last therapy given and development of biochemical recurrence was 17.5 months. All had elevated CA 125 levels at the time of PET/CT with mean level of 93.7 IU/ml (range: 6.5–558). Eighteen patients had prior lesions positive/suspicious for recurrence in the conventional imaging before FDG PET/CT. In FDG PET/CT tracer avid lesions (mean SUVmax 14.2) at the ovarian fossa was seen in only 6/39 patients. Tracer avid abdominal/pelvic visceral deposits (serosal, peritoneal), omental deposits, abdominal/pelvic lymph nodes, liver, lung, and brain lesions were noted in 11, 13, 26, 3, 2, and 1 patients, respectively. In addition, tracer avid ascites was noted in three patients. Two patients also had tracer avid lesions in the breast with axillary lymphadenopathy suspicious for development of second primary in breast. They were excluded from final analysis. Hence, in total, PET/CT showed positive for disease relapse in 32/37 (86.4 %) patients. The mean elevated CA 125 value in PET positive for recurrence patients was 103.4 ng/ml while in PET negative for recurrence was 47.9 ng/ml (P = 0.9). All except two patients succumbed to the disease (mean survival time of 36.4 months) out of the 18 patients in which telephonic follow-up was possible. Conclusion: FDG PET/CT had high diagnostic utility in patients with elevated CA 125 level, especially in asymptomatic as well as prior imaging negative patients.
| PP29: Diagnostic utility of Ga-68 DOTANOC positron emission tomography-computed tomography in the evaluation of neuroendocrine tumor of unknown primary and evaluation of pattern of metastasis | | |
Venkata Subramanian Krishnaraju, Rajender Kumar Basher, Bhagwant Rai Mittal
Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Background and Objectives: It is sometimes seen that patients present with metastatic foci of disease which turn out to be neuroendocrine tumors (NET) but do not have a diagnosed primary site of disease. This study is done to evaluate the diagnostic efficiency of Ga-68 DOTANOC positron emission tomography-computed tomography (PET/CT) in identifying the primary lesion in cases of patients presenting with metastatic lesions of NET without a known primary and to also evaluate the pattern of metastatic involvement in those patients. Materials and Methods: Retrospective evaluation of Ga-68 DOTANOC PET/CT studies performed from January 2015 to August 2018 was done, from which 87 patients were included in the study. The inclusion criteria included patients with lesions anywhere in the body, which on pathological evaluation turned out to be metastatic NET and were being evaluated to localize the primary and also to assess the extent of the disease. Patients in whom any form of prior surgery or systemic therapy was given for the same indication were excluded from the study. Results: Eighty-seven patients were included in the study, of which 48 were males and 39 females. They had a mean age of 53.5 (range 16–85) years and had pathologically proven lesions of NET which were suspected to be metastatic foci and with no obvious certain primary site on conventional imaging. The initial diagnosis of metastatic NET was made by sampling from different sites such as liver (n = 77), lymph nodes (n = 7), and bone (n = 3). The predominant site of lymph node metastases sampled was from the left supraclavicular node (n = 3). Of the liver lesions, majority were multiple in nature (n = 70) while few were solitary (n = 7). On imaging with DOTANOC PET/CT, tracer avidity was seen in 81 of those metastatic lesions while 6 were non avid. Among those 6 patients with nonavid metastatic lesions on DOTANOC, primary was not found in 4 patients, probably due to the poor level of differentiation and consequent poor somatostatin receptor expression in these lesions. On the whole, of the 87 patients imaged, primary site of malignancy was identified in 71 patients (81.6%) while no primary was identified in 16 patients (18.4%). The primary site was mostly unifocal (n = 67) while 4 patients had multifocal disease (n = 4) which was confined to the small bowel. 65/77 patients with liver lesions had a primary site identified and the most common site of primary was pancreas (n = 22/65, 33.8%), followed by small intestine (n = 19/65, 29.2%). Most common site in the small bowel was jejunum (n = 8). Of the patients with bone metastases as the index lesion of diagnosis (n = 3), primary was not found in 1 patient, while 1 lesion each was found in thyroid and bladder. While assessing the pattern of metastatic involvement, it was noted that of the patients with rectal primary (n = 8), seven patients (n = 7/8, 87.5%) had bone lesions. Similarly, of the 22 patients with pancreatic primaries which had a median SUVmax of 19.8 (interquartile range 18.08), it was found that eight patients had bone lesions, and of them, seven patients had a SUVmax in the primary of less than 19.8 (n = 7/8, 87.5%). Regional and distant lymph node involvement was seen in 64/87 patients (73.5%). Conclusion: Ga-68 DOTANOC PET/CT has a high diagnostic utility in identifying the primary in patients who present with secondary metastatic lesions of NETs. The liver is the most common site of metastases in patients with occult primary, and most of them have their source of primary in the pancreas and small bowel. Lymph node involvement is also seen in majority of these patients. Rectal NETs seemed to have a higher predisposition for presenting with skeletal lesions, as did pancreatic lesions with a lower amount of somatostatin receptor expression.
| PV19: Role of positron emission tomography/computed tomography in detecting hidden malignancies at the time of diagnosis of membranous nephropathy: Case report | | |
Saloni Mehta
Grecian Super specialty Hospital, Chandigarh, India
Background and Objectives: Membraneous nephropathy (MN) is the most commonly occurring nephrotic syndrome in adults as well as the most common paraneoplastic nephropathy associated with solid tumors, and it is mostly associated with gastrointestinal system and lung carcinomas. Search for an occult malignancy in MN has presented special challenges. Accurate diagnosis is important as the treatment of paraneoplastic glomerulonephritis is very varied from that of idiopathic ones. Materials and Methods: In the current report, a case of a patient who presented with proteinuria and edema was referred for whole body 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (PET-CT) scan, which showed a hypermetabolic cavitatory lesion in the lung with other sites of metastases, favoring lung mitotic etiology, and was thereafter histopathologically proven to be lung cancer. Active cancer is present in all patients with paraneoplastic MN. In numerous patients, the paraneoplastic MN and cancer diagnoses are made within 1 year of each other. The treatment of paraneoplastic syndromes is usually associated with the treatment of primary malignancy. There are conflicting data on which treatment modality is more suitable. In conclusion, further studies are required to determine the actual incidence of cancer in patients with nephropathy, explain the physiopathological association between cancer and nephropathy and to determine the most suitable treatment approaches. Conclusion: A potential cancer surveillance that the malignancy screening either through conventional or by PET-CT at the diagnosis of MN led to an early diagnosis and curative treatment.
| PV20: Tumor characteristics and metabolic quantification in carcinoma breast | | |
I. P. Dubey, A. Jain1, S. K. Agrawal2, A. Sharma2, M. G. Vishnoi3
Command Hospital Lucknow, Lucknow, Uttar Pradesh, 1Command Hospital Pune, Pune, Goa, Maharashtra, 2Command Hospital Kolkata, Kolkata, West Bengal, 3Army Hospital R&R, New Delhi, India
Background and Objectives: In India, carcinoma breast is the most common cancer among urban women population and second most common cancer after carcinoma cervix in rural areas. One in 22 women in India develops carcinoma of the breast in their lifetime. Fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in breast cancer usually indicates the degree of tumor metabolism and hence can predict its behavior and prognosis. On the other hand, the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) or neu state of breast cancer is a biomarker that provides important prognostic information in addition to predicting response to therapy. The main objective of this study is to assess whether a correlation exists between 18F-FDG uptake in untreated cases of breast cancer, their receptor status (ER, PR, and HER-2 or neu), tumor histology, and tumor size. Materials and Methods: Sixty consecutive female patients, with biopsy-proven primary breast cancer, were enrolled in this prospective study for whom 18F-FDG positron emission tomography-computed tomography scan was done in the Department of Nuclear Medicine. Results obtained were analyzed using appropriate statistical tests (t-test and Pearson Chi-square tests), and interpretation was made with 95% confidence level. Results: In our series, a positive correlation between tumor size, high tumor grade, and standardized uptake value (SUV) was found. Tumors with positive receptor status for ER, PR, and HER-2/neu had statistically insignificant lower maximum SUV (SUVmax) values than their negative counterparts. Triple-negative breast tumors (ER−, PR−, and no overexpression of HER-2/neu) are currently a subject of major interest because of their aggressiveness, poor prognosis, and lack of targeted therapy. Based on receptor status, when the SUVmax of the group with triple-negative receptor status (ER−/PR−/HER-2/neu−) was compared to rest of the patient group, it was seen that patients with negative receptor status had significantly higher mean SUVmax values. Conclusions: We have inferred that in patients with breast cancer, various biological parameters such as tumor size, grade, histology, and hormonal receptor status have different impact on tumor metabolic activity.
| PV21: Assessment of biochemical recurrence of prostate cancer with C-11 choline | | |
Ashutosh Parashar, Sanjay Gambhir, Man Mohan Singh, A. H. Nazar, Mnish Ora, Amitabh Arya, S. Barai, P. K. Pradhan
Department of Nuclear Medicine, SGPGI, Lucknow, Uttar Pradesh, India
Background and Objectives: To evaluate the diagnostic performance of 11C-choline positron emission tomography-computed tomography (PET/CT) in restaging of biochemical recurrent prostate cancer (PC). Materials and Methods: Thirty-eight patients with recurrent PC underwent a non-contrast enhanced 11C-choline PET/CT. Whole-body PET CT acquisition was performed 2 min after ~20 mCi of C11-choline intravenous administration. Imaging datasets were assessed for the presence of local recurrence, lymph node, and bone metastases. Results: In the current study, the mean age of patients was 68.4 years. Out of these patients, 11 had undergone bilateral orchidectomy, 14 had undergone radical prostatectomy, and 10 were on anti-androgen therapy. Postprostatectomy, average serum prostate-specific antigen (S. PSA) was 33.8 ng/dl and in those with intact prostate was 124.8 ng/dl. Postorchidectomy, S. PSA was 39.04 ng/dl and those without had and average PSA of 111.8 ng/dl. Average S. PSA on those on anti-androgen therapy was 24.9 ng/dl and those without had 125.5 ng/dl. Prostatic lesions were found in 21 patients and regional lymphadenopathy was found in 17 patients. Thirteen patients were positive for mediastinal/retroperitoneal lymphadenopathy. Sclerotic bone lesions were found in 15 patents of which 8 patients showed significant C-11 choline avidity. Mean SUVmax of prostate was 3.1 and of pelvic lymph nodes was 2.6. Other than pelvic lymph nodes which showed choline uptake, there average SUV was 2.1. Sclerotic bone lesions with choline uptake were noted in 8 patients with average SUVmax of 5.2. Conclusion: In the current study, we were able to identify local and regional recurrence in patients and correctly restage the systemic spread % patient. Hence, choline is also helpful in assessing the effectiveness of anti-androgen therapy or in identification of those who shall need the same. 1C-choline PET/CT is a robust imaging modality for restaging biochemical recurrent PC. It stratifies patients on the basis of local and systemic burden of disease. Thus, the further management in term of local radiotherapy, surgeries or systemic therapies may by be planned. Not only it provides good diagnostic value for detecting local recurrence, but it also helps in radiotherapy planning, either for dose escalation or exclusion of selected sites.
| PV22: Primary central nervous system lymphoma presenting as cauda equina syndrome: Pictorial essay of two case reports: An institutional experience | | |
Surekha Yadav
Army Hospital, Research and Referral, New Delhi, India
Background and Objective: Primary central nervous system (CNS) lymphoma is rare tumor, accounting for 1%–7% primary brain tumors and 1%–2% of NHL. Primary lymphoma of spinal cord is even rare with <1% case in adults. We report two such cases from our institute. The objective of this presentation will be to describe the clinical features and the role of positron emission tomography-computed tomography (PET-CT) in the management of primary CNS lymphoma along with review of literature. Results and Discussion: Two cases of primary CNS lymphoma presenting as cauda equina syndrome are discussed. The cases were identified and routine hematological ad biological investigations along with biopsy, cerebrospinal fluid analysis, magnetic resonance imaging, and PET-CT were carried out at the institutional level. We followed up these cases. They underwent chemotherapy along with Interim and Post-treatment response assessment PET-CT scans. The PET-CT findings before, interim and after treatment were analyzed in the light of existing literature. In this presentation, clinical features, pathological findings, and PET-CT findings are discussed for the above-mentioned cases.
| PV23: Theranostic role of chemokine receptor imaging in multiple myeloma patients | | |
Shivani Madaan, Jaya Shukla, Shashank Singh, Rakhee Vatsa, Priya Bhusari, Rajender Basher, Bhagwant Rai Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Background and Objectives: Chemokine receptor (CXCR4) belongs to a G-protein coupled receptors family. A variety of cells express CXCR4 during the development, but its overexpression can be seen in various malignancies such as lung, breast, multiple myeloma, and leukemia. The overexpression has been identified as adverse prognostic factor and may be exploited as a therapeutic target. Hence, various synthetic analogs of natural ligands have been developed. The study aims to evaluate the utility of Ga-68 chemokine analog (CXC) for in vivo imaging of CXCR4 and compare with metabolic imaging tracer, 18F-labeled fluoro-2-deoxyglucose (F-18 FDG). Materials and Methods: CXC was prepared in-house in semi-automated fluidic module. Ga-68 was freshly eluted in 0.05 M HCL from Ge-68-Ga-68 generator. Chemokine peptide analog (20 μg), dissolved in sodium acetate buffer at pH 4.0 was incubated at 95°C for 10 min. Ga-68 CXC was separated from the solution by solid phase extraction (C-18) in 1 ml 50% ethanol. C-18 was washed with normal saline. The pH was maintained by adding sodium acetate buffer and passed through 0.22 μ filter. RadioITLC was performed to check radiochemical purity. Apyrogenicity was tested as automated PTS. The clearance from institutional ethics committee and informed written consent from patients was obtained before intravenous injection of Ga-68 CXC. A total of eight multiple myeloma patients (mean age 55 years, age range 39–70 years, 5 male and 3 female) were recruited. F-18 FDG and CXC positron emission tomography-computed tomography (PET/CT) scans were done. CXC PET/CT was acquired at low current (10 mA). Average SUVmax of five bone lesions and extramedullary lesions on both scans were compared. Results: The total preparation time of CXC was 20 min. Radiolabeling yield of >95% with >99% radiochemical purity was achieved. Residual ethanol content was below permissible limit. All the samples were found to be sterile on sterility test and endotoxin content was less than 2.53 EU/ml. FDG was synthesized on automated module. The SUVmax of marrow uptake in FDG and CXC was 1.1–6.2 and 2.0–18.6. The average SUVmax of bone lesion on FDG and CXC was 3.1–22.3 and 4.1–20.8. Seven out of eight patients showed bone lesions on FDG, in one patient FDG was done 1 year back and probably bone lesions were not present during the scan. However, six patients showed positivity on CXC and diffuse uptake was noted in entire visualized skeleton without any morphological abnormality in two patients. Conclusion: Both CXC and FDG play an important role in assessing disease burden. CXC being receptor specific has additional role in targeted therapy planning.
[TAG:2]PV24: Prostate-specific membrane antigen expression in metastatic transitional cell carcinoma detected on Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography scan: A potential molecular target for imaging and therapy in transitional cell carcinoma[/TAG:2]
Shreyas R. Kudachi, Pankaj Kumar, Vikram R. Lele, Dinesh Kumar, R. Sudha
Department of Nuclear Medicine and PET, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Prostate-specific membrane antigen (PSMA), a type II membrane protein, expressed on prostate epithelial cells and upregulated in prostate carcinoma, has enabled to develop imaging for prostate cancer and targeted therapy. However, PSMA is not specific to the prostate gland and is expressed in other normal tissues and malignancies such as transitional cell carcinoma (TCC) among others. Studies have shown that PSMA protein is consistently detectable in normal and malignant urothelium. However, PSMA expression is much weaker than in prostate-derived tissues. Intense PSMA expression in such malignancies is most likely due to neovascular endothelial cells. Magnetic resonance imaging (MRI) and computed tomography (CT) are limited in identifying micrometastases and impractical in whole-body metastatic workup. 18F-flourodeoxyglucose positron emission tomography-CT (FDG PET/CT) scan, on the other hand, offers marginally better results. PSMA expression in TCC can be exploited by PSMA-targeted radiotracers in detecting lesions offering higher sensitivity. Standard of care of TCC is surgery if localized followed by chemoradiation and immunotherapy. Metastatic TCC was associated with a median survival of 4 months as compared to 18 months in patients without visceral metastases. Although few cases of urothelial carcinoma positive on PSMA PET/CT have been reported, we are trying to exploit PSMA expression in TCC on Ga-68 PSMA PET/CT to look for feasibility of using targeted radioligand therapy. Materials and Methods: A 65-year-old male with histologically proven urothelial carcinoma of terminal right ureter underwent radical cystectomy with ileal conduit. Serial FDG PET/CT scans suggested poor response to multiple lines of chemoradiation and immunotherapy. In this progressive disease of TCC, poor response to standard line of care was strong predictor of poor survival. Hence, he was investigated further to detect PSMA expression in metastatic lesions to explore the possibility of targeted PSMA therapy. 3 mCi of Ga-68 PSMA was injected intravenously to patient and was scanned after 60 min on dedicated 16 slice PET-CT (GE-DISCOVERY IQ 5 ring scanner). Results: Ga-68 PSMA PET/CT revealed multiple soft tissue deposits, nodal and skeletal metastases with moderate-to-high-grade PSMA expression. Conclusion: With encouraging response rates and a low toxicity profile of radioligand therapy in prostate cancer using Lu-177- and Ac-225-labeled PSMA ligands, the same could be applied for other malignancies with PSMA expression, who have exhausted other treatment options. As with our understudy Ga-68 PSMA PET/CT is better at picking up many more lesions than FDG PET/CT and thus opening avenues for application of targeted PSMA therapy.
| PV25: Flourodeoxyglucose positron emission tomography-computed tomography in T-cell lymphoma | | |
Rashmi Angadi
Department of Nuclear Medicine, PETCT and Radionuclide Therapy, KLES Dr Prabhakar Kore Hospital and MRC, Belagavi, Karnataka, India
Background: T-cell lymphomas comprise heterogeneous group of lymphomas, accounting for 12% of all cases of NHL. Although relatively rare, they have a poorer prognosis than B-cell lymphomas. Literature on the role of flourodeoxyglucose positron emission tomography-computed tomography (FDG PET CT) in T-cell lymphomas is sparse. Aims and Objectives: The purpose of this study is to quantify the avidity of FDG in the various histologic subtypes of T-cell lymphoma, to highlight the pattern of imaging findings associated with specific disease patterns, and to describe the utility of 18F FDG PET CT in initial staging, assessment of response to therapy, and restaging. Materials and Methods: A retrospective review of 15 patients with T-cell lymphoma who underwent PET CT examination for over a period of 2 years was undertaken. Whole-body PET CT scan was performed after 60 min with GE discovery STE PET/CT. Sites of the disease involvement were documented according to nodal, cutaneous/extranodal, and visceral involvement. 10 mCi of 18F FDG injected. Interpretation of the PET CT and response assessment was carried out as per the IWC PET criteria. Results: Fifteen patients with T-cell lymphomas were included. Fourteen PET scans were performed for initial staging, 10 of these patients also underwent second PET scan after completion of chemotherapy for assessment of response to therapy, and one patient underwent PET CT only for restaging during recurrence. Patterns of disease based on sites of lesions at initial staging were noted: 7% had cutaneous involvement; 7% had nasal cavity and nasopharyngeal (extranodal involvement); 86% had nodal involvement; 20% had visceral involvement. Cutaneous T-cell lymphoma patients showed the SUVmax of 2.5 and patient with visceral involvement showed SUVmax of 23. In the posttreatment PET CT, 70% (7/10) patients showed complete response, 10% (1/10) showed stable disease, and 20% (2/10) showed progressive disease. Conclusion: T-cell lymphoma subtypes evaluated in this study show variable FDG avidity depending on the histological subtype and pattern of disease. FDG PET CT is useful in initial staging, assessment of response to therapy, and restaging during the recurrence.
| PV26: Comparison of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography and contrast-enhanced computed tomography for response assessment in patients with colorectal liver metastases on follow-up postchemotherapy | | |
Alok Dixit, B. A. Krishna, Nirav Thakker1
Departments of Nuclear Medicine and 1Radio diagnosis, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India
Objectives: The purpose of this study was to compare efficacy of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) versus CECT (contrast-enhanced CT) in chemotherapy response evaluation for patients with colorectal liver metastases (CRLM). Materials and Methods: A total of 34 patients (25 males, 9 females; 27–78 years, mean 57.29 ± 13.026 standard deviation) with suspected or diagnosed cases of CRLM were recruited for the study based on specific inclusion and exclusion criteria. All patients were interviewed and are recruited in the study only after oral and written consent prospectively as they were referred for the whole-body FDG-scan which was followed by data acquisition and data analysis on Phillips Truflight PET-CT with Time of Flight imaging, Philips Medical Systems with 16 slice helical CT. A follow-up FDG PET CT scan was done postchemotherapy, for response evaluation, and response was evaluated based on the RESIST 1.1 and PERCIST criteria for CECT and PET/CT, respectively. All patients who responded and nonresponded on follow-up PET/CT were followed up further with telephone interview after 3 months for assessment of actual overall disease response (ODR). Data were analyzed using professional statistics package EPI Info 7.0 version for Windows. Appropriate test of significance was used depending on nature and distribution of variables such as independent t-test for numerical variables and kappa test for categorical variables. P < 0.05 was considered statistically significant. Results: PET/CT predicted 30 out of 34 patients (88.24%) as responders (metabolically complete and partial response) compared to only 7 responders (20.58%) on CECT. CECT predicted 27 patients (79.41%) as nonresponders compared to only 4 (11.76%) nonresponders on PET/CT. 73% patients showed response on clinical follow-up compared to 27% as nonresponders, which is close to the prediction of response by PET/CT. On assessing the agreement between PET/CT response and ODR by using Cohen's Kappa test, we found that there is good agreement between and ODR (k-coefficient, 0.54) with P < 0.001; in contrast, there is poor agreement between CECT response and ODR using the same Cohen's Kappa test (k-coefficient, 0.079) with P = 0.41), suggesting change in quantitative parameters (SUVmax) of PET/CT are more predictive of ODR. Hence, predictive value of PET/CT for ODR is more than that with CECT alone. Conclusion: Metabolic imaging using FDG PET-CT has a good predictive value for ODR for treatment response assessment. On the other hand, discordance is noted with overall disease response when evaluated with conventional size criteria (RESIST 1.1). A larger study with a larger group of patients will be needed in future for more purposeful conclusions.
| Radionuclide Therapy Track | | |
| OP26: Sandwich chemo-PRRT protocol in advanced aggressive gastroenteropancreatic neuroendocrine tumors: Evaluation of clinical response | | |
Rahul Vithalrao Parghane, Vikas Ostwal1, A. Ramaswamy1, Sharmila Banerjee, Sandip Basu
Radiation Medicine Centre (BARC), TMH, 1Departments of Medical Oncology, TMH, Mumbai, Maharashtra, India
Background and Objectives: Aggressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) present clinical challenges, especially related to disease control and survival. PRRT is used for SSTR expressing metastatic/advanced well-differentiated NET, whereas chemotherapy is used in high-grade, poorly differentiated, and aggressive advanced NET. In intermediate, gray zone exists with tumors demonstrating high 18F-labeled fluoro-2-deoxyglucose (18F-FDG)/68Ga-DOTATATE uptake on dual tracer positron emission tomography/computed tomography (PET/CT), where a combined approach can be more logical and rational. Objective: The aims of the study were to evaluate feasibility of sandwich chemotherapy with PRRT as chemo-PRRT in treating 18F-FDG avid aggressive GEP-NET and also to evaluate response rate, progression free survival (PFS), overall survival (OS), and clinical toxicity of sandwich chemo-PRRT. Materials and Methods: A total of 19 patients with metastatic/advanced 18F-FDG and SSTR avid GEP-NETs were included and analyzed retrospectively. 177Lu-DOTATATE PRRT was administered intravenous with 150–200 mCi per cycle. CAPTEM chemotherapy was administered after 1 week of PRRT with oral capecitabine 1500 mg/m2 for 14 days (days 1–14) and oral temozolomide 200 mg/m2 once daily for 5 days (days 10–14) followed by 2-week rest period and another CAPTEM cycle given followed by PRRT at 3 months. Thus, between two cycles of PRRT, two cycles of CAPTEM was sandwiched. Response evaluation included molecular/structural imaging (68Ga-DOTATATE and 18F-FDG PET/CT), symptomatic and biochemical responses in all patients. Patients were classified as responders (complete response, partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]) using RECIST 1.1 response criteria and also evaluated for clinical toxicity related to chemo-PRRT. Results: Of the 19 patients, 3 patients (15.7 %) died with 1 year OS of 86.8% (confidence interval [CI] 69%–100%) and 2 years of 78.9% (CI 57%–100%) after first chemo-PRRT. PR in 5 patients (26%), SD in 10 patients (52%) and PD in 4 patients (22%) with PFS at 1 year 72.9% (CI 50%–96%), 2 years 58.3% (CI 32%–84%), 3 years 43.7% (CI 12%–75%) and median PFS of 28 months following chemo-PRRT and P = 0.009 between PFS of responders versus nonresponders. Protocol was tolerated well in all patients with no major hematological and renal toxicity. Conclusions: Sandwich CAPTEM with PRRT (as chemo-PRRT) is a well-tolerated, effective regimen with durable response rate in aggressive advanced 18F-FDG avid disease in GEP-NET patients. Most of patients achieved significant tumor control and relief of symptoms with combined benefit of both chemotherapy and PRRT, resulting in prolonged PFS and OS in advanced and unfavorable disease with no significant toxicity as compared to single agent PRRT or chemotherapy.
| OP27: Overview of peptide receptor radionuclide therapy with 177Lutetium-DOTATATE in our institution: 4 years' experience | | |
David Mathew, Julie Hephzibah, Nylla Shanthly, Regi Oommen
Christian Medical College Hospital, Vellore, Tamil Nadu, India
Background and Objectives: There are very limited treatment options in patients with inoperable and metastatic neuroendocrine tumor (NET) and medullary thyroid carcinoma (MTC). Peptide receptor radionuclide therapy (PRRT) with 177Lutetium-DOTATATE is a recently upcoming standard option in the management of these. Materials and Methods: Patients with metastatic NET and MTC who underwent lutetium-DOTATATE therapy during the period from May 2014 to May 2018 in our institution, which is a tertiary care center, were analyzed in this retrospective study. Follow-up imaging studies including 68Gallium-DOTATATE PET/CT scans and biochemical response (serum calcitonin, chromogranin A, CEA, and gastrin levels) as compared to baseline were determined to assess response to treatment. Our institutional practice was to use 177Lu-based somatostatin analogs using 68Ga-DOTATE sufficient tumor uptake as a patient eligibility criteria. Kidney protection was done with amino acid infusion after evaluating for baseline kidney function based on a renogram. Results: An average of 136 mCi was given per dose. Totally, 35 patients (32 with NET and 3 with MTC) were analyzed (male = 27; female = 8), out of which 22 (62%) completed 4 doses of 177Lutetium-DOTATATE, 4 (11%) completed 3 doses, 5 (14%) received 2 doses, and 4 (11%) defaulted after first dose. There was a fall in biochemical markers in 9 (26%) patients while it was found to be increasing in the other 13 (37%) patients. 13 (37%) had no data. Imaging done after 7 weeks of the last dose revealed regression in 7 (20%) patients, stable disease in 6 (17%) patients (2 MTC), and progression in 10 (29%) patients. Posttherapy imaging is awaited in 9 (26%) patients. 3 (9%) were lost to follow-up. Symptomatic improvement was noticed in 28 (80%) patients while 7 (20%) reported clinical worsening. There was no death reported due to the treatment – during or immediately posttreatment. Conclusion: Our study showed that treatment with 177Lutetium-DOTATATE should be offered as a first-line treatment option in the management of advanced NET and MTC, considering the limited alternative treatment modalities with its significant morbidity. A good treatment response (60% of patients benefitted overall) was seen to justify the continuing importance of lutetium-DOTATATE therapy in the forefront of management of inoperable and metastatic NETs.
| OP28: 177Lu-prostate-specific membrane antigen radioligand therapy in aggressive metastatic castration-resistant prostate carcinoma following multiple treatment failures | | |
Sonam Suman
Radiation Medicine Center (BARC), TMH Annex, Mumbai, Maharashtra, India
Background and Objectives: Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly upregulated in prostate cancer. Progression to androgen independence is the main cause of death in prostate cancer patients. PSMA expression levels are directly correlated to androgen independence, metastasis, and higher grade tumors and are attractive target for diagnosis and therapy of metastatic prostate cancer. The study aims to evaluate the utility of 177Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC) who progressed with other therapies, in terms of response rate on three scales, median progression-free survival, overall survival, and toxicity assessment. Materials and Methods: A total 25 patients of mCRPC progressed on other treatments who underwent at least 2–4 cycles of 177Lu-PSMA. (dose range: 120–150 mCi/per cycle) at 10–12 weeks interval were retrospectively analyzed. The therapy response was analyzed for clinical, biochemical (serum prostate-specific antigen level) and molecular scan response, median overall survival, and median progression-free survival with hematological and renal toxicity assessment. Results: The study population was divided into two groups: those who received (a) 177Lu-PSMA RLT alone (Group A; n = 21) and (b) those with concurrent 177Lu-PSMA therapy + abiraterone (Group B; n = 4) and response of these groups were analyzed separately. Both groups received newer anti-androgens and chemotherapy (including docetaxel and cabazitaxel). Prior treatment history: (a) administration of any hormonal therapy-25, (b) abiraterone-4, (c) chemotherapy-17, and (d) external radiotherapy-13; two patients volunteered to be treated upfront. Among Group A (n = 21), at the time of analysis, 71% were alive (n = 15) and 28% died (n = 6). Complete response (CR) was noted in 5 (24%), partial response (PR) in 6 (28%), stable disease (SD) in 3 (14%) and progressive disease (PD) in 7 patients (34%) on symptomatic response evaluation; CR was noted in 9 patients (43 %), PR in 3 (14 %), PD in 9 (43%) on biochemical response evaluation; PR in 4 patients(19 %), SD in 11 (53%), PD in 6 patients (28%) on imaging. Of Group B (n = 4), symptomatic response with CR was noted in 1 patient (25%), PR in 1 (25%), SD in 1 (25%), and PD in 1 patient (25%). On biochemical scale, CR was noted in 2 (50%), SD-1 (25%), and PD-1 patient (25%). Scan response was noted as PR-2 patients (50%) and PD-2 patients (50%). With 177Lu-PSMA therapy, median overall survival was 8 months and median progression-free survival was 6 months. Conclusion: 177Lu-PSMA therapy was found effective in disease control and well tolerated with a low toxicity profile in patients with aggressive mCRPC and likely to have an important role in future.
| PP30: Comparative evaluation of therapeutic efficacy of equidose of 153Sm-EDTMP and 177Lu-EDTMP for bone pain palliation in patients with skeletal metastases | | |
Sarika, Baljinder Singh, Bhagwant Rai Mittal, Ashwani Koul
Department of Nuclear Medicine and PET, PGIMER, 1Department of Biophysics, Panjab University, Chandigarh, India
Objective and Methods: The present study evaluated the comparative therapeutic efficacy using pain scoring and absorbed dose to the metastatic lesions with equidose of 153Sm-EDTMP and 177Lu-EDTMP for bone pain palliation in patients with multiple skeletal metastases. The patient's serial imaging data after radiopharmaceutical administration were exported to the personal computer for the absorbed dose calculations on the “metastatic lesions” and different organs. Results: The mean administered dose of 153Sm-EDTMP and 177Lu-EDTMP was 58.25 ± 11.34 mCi and 52.30 ± 15.12 mCi, respectively. Both 153Sm-EDTMP and 177Lu-EDTMP exhibited rapid blood clearance and good urinary excretion with only 20.0%–25.0% of the injected radioactivity of each of the radiopharmaceutical being excreted within the first 3 h after intravenous administration. The mean absorbed dose to the bone from 177Lu-EDTMP was observed to be 5.26 ± 1.40 mSv/MBq which was insignificantly higher than that (4.04 ± 2.47 mSv/MBq) observed in 153Sm-EDTMP. The response rate for each radionuclide in terms of a significant reduction in pain score was evaluated as about 80.0%. No statistically significant correlation was observed between the absorbed dose to the metastatic sites and pain score. The mean absorbed doses received by the metastatic sites were 6.22 ± 4.21 mSv/MBq and 6.92 ± 3.92 mSv/MBq in 153Sm-EDTMP- and 177Lu-EDTMP-treated patients, respectively. Conclusion: Both the radiopharmaceuticals have shown similar normal human biodistribution and delivered the same radiation dose to the various organs and therefore can be used interchangeably depending upon the availability in a given center.
| PP31: Rhenium-188 hydroxyethylidinediphosphonate for bone pain palliation therapy: Initial clinical experience | | |
S. Yogananth, Ajit S. Shinto1, S. Arun Pandian1, E. R. Radhakrishnan1, V. J. Arnold1, F. R. Kingsley1, Raghi P. Jose1, K. K. Kamaleswaran1, B Surya1
Kovai Medical Centre Research and Educational Trust, 1Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
Background and Objectives: 188Rhenium-hydroxyethylidinediphosphonate (18Re-HEDP) is a clinically established radiopharmaceutical for bone pain palliation of patients with metastatic bone cancer. Herein, the effectiveness of 188Re-HEDP for the palliation of painful bone metastases was investigated in an uncontrolled initial trial in 48 patients with different types of advanced cancers. Materials and Methods: A group of 48 patients with painful bone metastases of lung, prostate, breast, renal, and bladder cancer was treated with 2.96–4.44 GBq (80–120 mCi) of 188Re-HEDP. Results: The overall response rate in this group of patients was 89.5%, and their mean visual analog scale score showed a reduction from 9.1 to 5.3 (P < 0.003) after 1 week posttherapy. Serious adverse effects were not reported by the patients, either during intravenous administration or within 24 h postadministration of 188Re-HEDP. Flare reaction was observed in 54.2% of patients between day 1 and day 3. There was no correlation between flare reaction and response to therapy (P < 0.05). Although bone marrow suppression was observed in patients receiving higher doses of 188Re-HEDP, it did not result in any significant clinical problems. Conclusion: The present study confirmed the clinical utility and cost-effectiveness of 188Re-HEDP for palliation of painful bone metastases from various cancer types in developing countries.
| Thyroid Track | | |
| OP29: Efficacy of radioactive iodine therapy in hyperthyroidism of the elderly | | |
D. Chakraborty, Nishikant Avinash Damle, Chandrasekhar Bal, M. Prabhu, A. Prasanth, K. S. REddy, S. Arora, A. Behera, Praveen Kumar
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: Hyperthyroidism in the elderly is associated with significant morbidity, hence needs early definitive cure. Radioactive iodine therapy (RAIT) is the treatment of choice for autonomous functioning thyroid nodule (AFTN), toxic multinodular goiter (TMNG), and a preferred therapy for Graves' disease (GD) in the elderly. We aimed to evaluate the efficacy of RAIT in an elderly age group ≥ 65 years. Materials and Methods: Retrospective review of medical records of 37 hyperthyroid patients (female 26 and male 11) who visited Department of Nuclear Medicine Thyroid Clinic of AIIMS, New Delhi, from January 2015 to August 2017 for RAIT was performed. Among 37 patients (age range 65–80 years, median age 67 years), 21 were diagnosed as GD, 13 patients had TMNG, and 3 patients had solitary AFTN. 34/37 patients presented with typical toxic features and rest 3/37 presented with apathetic hyperthyroidism. Median duration of illness before presentation was 2 years (range 2 months–30 years). Goiter size as per the WHO grading was 0 in 13, grade 1 in 11, grade 2 in 9, and grade 3 in 4 patients. One patient showed ophthalmopathy. 34/37 patients had received antithyroid drugs (ATDs) before radioiodine therapy, and 3 were drug naive. Average 24 h RAIU was 49.75% (range 14%–99%). Average first 131iodine dose was given 9 mCi (dose range 5–20 mCi) after making the patient as close to euthyoid as possible. Follow-up data of more than 1 year (median follow-up time 24 months, range 12–42 months) was available for 25 patients (14 GD, 9 TMNG, and 2 AFTN). Success of the RAIT was defined as a stable euthyroid or hypothyroid status at 12 months posttherapy. Results: Overall success rate of RAIT was 84% (21/25) patients. Twelve patients achieved euthyroidism, and 9 patients became hypothyroid. Rest 4/25 (16%) patients (3 GD and 1 TMNG) showed persistent subclinical hyperthyroidism at the end of follow-up period. Ten patients (8 having GD and 2 with TMNG) cured with single RAIT; 8 (1 GD, 5 TNMG, and 2 AFTN) with two doses, and 3 (2 GD and 1 TMNG) with three doses. 8/14 GD, 2/9 TMNG, and 0/2 AFTN were considered first-dose success. 78% (11/14) GD, 88% (8/9) TMNG and 100% (2/2) AFTN patients were biochemically cured at the end of 1 year. None of these 25 patients showed any significant adverse event during the follow-up of 1 year. Conclusion: RAIT is effective and safe in the treatment of elderly hyperthyroidism.
| OP30: To evaluate role of sodium valproate and thalidomide therapy in treatment of de-differentiated thyroid carcinoma | | |
Meghana Prabhu, N. A. Damle, Dhritiman Chakraborty, K. S. Reddy, A. Prashanth, S. Arora, Praveen Kumar, A. Behera, Chandra Sekhar Bal
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: Re-differentiation therapy is considered potential treatment option in de-differentiated thyroid carcinoma patients, who are otherwise largely untreatable. Few drugs have been used over the last two decades for re-induction of sodium iodide symporter (NIS) in such patients. We aim to evaluate two different drugs (sodium valproate and thalidomide) in the treatment of de-differentiated thyroid carcinoma. Materials and Methods: We retrospectively evaluated the role of thalidomide (n = 26) and sodium valproate (n = 11) in cases of de-differentiated thyroid carcinoma with negative 131-I whole-body scan (WBS), raised thyroglobulin (Tg), and/or clinically evident disease. Thalidomide was given in a median dose of 200 mg (range 100–800 mg) and sodium valproate at a dose of 300 mg TID. Results: For thalidomide, the median age of patients was 45 years (range 21–65 years). Twenty patients had papillary while six had follicular thyroid carcinoma. Mean duration of therapy was 10.3 months. Mean radioiodine given before starting thalidomide was 202.5 mCi. Tg decreased in 18 patients and increased in 5 patients at the end of therapy, 1 patient showed no change, and 2 patients were lost to follow-up. Radioiodine uptake was seen in 5 patients, while majority (n = 11) showed no uptake, WBS was not acquired in 8 patients, and 2 cases were lost to follow-up. Based on Tg and clinical parameters, 8 patients had progressive disease, 5 stable disease, and 11 partial response. Thalidomide was stopped in 3 patients due to adverse effects. For sodium valproate, median age of patients was 45 years (range 31–61 years). Nine patients had papillary while 2 follicular thyroid carcinoma. Mean duration of therapy was 12.3 months. Mean radioiodine given before starting sodium valproate was 173 mCi. Tg decreased in 6 patients and increased in 4 patients at the end of therapy and one patient was lost to follow-up. Radioiodine uptake was demonstrable in 7 patients ranging from faint uptake to good uptake, 2 patients showed no uptake, WBS was not acquired in 1 patient, and 1 case was lost to follow-up. Based on Tg and clinical parameters, 4 patients had progressive disease, 2 stable disease, and 4 partial response. Of the seven patients with re-induction of radioiodine uptake, 3 had biochemical progression, 2 had good partial response, and 2 had stable disease. Conclusion: Our findings suggest that thalidomide and sodium valproate therapy may result in re-induction of uptake in some patients, but its exact clinical utility can be known only by a large prospective cohort study with long-term follow-up.
| OP31: Role of Ga-68 prostrate-specific membrane antigen positron emission tomography-computed tomography scan in anaplastic and medullary thyroid cancer | | |
T. Kishan Subudhi, Nishikant Avinash Damle, Geetanjali Arora, Meghana Prabhu, Madhavi Tripathi, Chandra Sekhar Bal, Rajeev Kumar1, C. Amit Singh1, Karan Madan2, Piyush Ranjan3, Ritesh Kumar4, Shipra Agarwal5
Departments of Nuclear Medicine 1ENT, 2Pulmonary Medicine, 3Surgery, 4Radiotherapy and 6Pathology, AIIMS, New Delhi, India
Background and Objectives: Anaplastic thyroid cancer (ATC) is the most aggressive human malignancy and the major reason for mortality is local infiltration of airway/esophagus/great vessels of the neck. Local palliation, therefore, is of prime importance. Recently, the expression of prostate-specific membrane antigen (PSMA) has been reported in nonprostate malignancies including thyroid cancer. Furthermore, because of the limited therapeutic options in ATC as well as medullary thyroid cancer (MTC), avidity to Ga-68-PSMA might provide theranostic options. Materials and Methods: Fourteen nondifferentiated thyroid cancer patients were included in the study. All patients underwent 68Ga-PSMA positron emission tomography-computed tomography (PET/CT) scan postinjection of 3–5mCi of 68Ga-PSMA-HBED-CC intravenously and whole body + regional scans were acquired 45–60 min postinjection (BiographmCT PET/CT scanner, Siemens Inc.). The scan was analyzed qualitatively as well as quantitatively. SUVmax of tumor, liver, mediastinum, and nodes and metastatic sites (with highest uptake) were calculated. Scoring of uptake (1–5) in primary tumor, nodes, and metastatic sites was done with reference to uptake in mediastinum and liver such that 1<mediastinum; 2=mediastinum; 3> mediastinum but <liver; 4=liver; 5> liver. Significance of uptake in primary tumor, with relation to mediastinum and liver, was determined by applying t-test/ANOVA test. Results: Fourteen patients (age: 35–68 years; 8 male; 6 female) were included, of which 10 patients had ATC while 4 patients had MTC. Six patients underwent surgery before the scan, of which 2 (1 each of ATC and MTC) had no visible residual mass on PET/CT. Twelve patients showed uptake in primary tumor (mean SUVmax = 14.6). All the 12 patients had a score 3 in primary tumor. Details of scoring in primary, nodes, and metastatic sites are given in [Table 1]. While nodal metastasis was present in all the 12 patients (mean SUVmax = 8.56), distant metastasis was present in 9 patients (mean SUVmax = 5.96). The tumoral uptake was significantly higher with relation to mediastinum (P = 0.0006) and difference in tumoral uptake approaching to significance with relation to liver (P = 0.058). Conclusion: Grade 3 and above uptake was seen in the primary in 12 of the 14 patients. Although adequate PSMA uptake is seen in most of the ATCs and MTCs, whether it translates into clinical benefit is a matter of debate since the uptake is neovascular rather than tumoral. However, our study suggests that this issue needs further validation.
| OP32: Is pre-131I-treatment anti-thyroglobulin antibody measurement significant in patients with differentiated thyroid cancer with synchronous lymphocytic thyroiditis? | | |
Tinu Thadiyananickal Lukose, Ashwani Sood, Bhagwant Rai Mittal, Anish Bhattacharya, Ashwin Singh Parihar, Anwin Joseph Kavanal, Harpreet Singh
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Background and Objectives: To correlate baseline elevated anti-thyroglobulin antibody (ATA) in patients of differentiated thyroid cancer (DTC) with histopathology of total thyroidectomy specimen showing features of thyroiditis and whether it has any statistically significant difference with nonthyroiditis histology. Materials and Methods: Data of 245 patients with DTC posttotal/completion thyroidectomy (from February 2016 to July 2018) were retrospectively analyzed. Patients who did not have a pre-131I-treatment thyroglobulin and antithyroglobulin values were excluded. The patients were grouped into thyroiditis-positive and thyroiditis-negative groups based up on the presence of lymphomononuclear inflammatory infiltration in histopathology of the thyroidectomy specimen. Patients were considered positive for thyroiditis if there was moderate to severe lymphomononuclear infiltrate in the background of thyroid carcinoma and negative when there was absence of the same. Results: Patient group with thyroiditis comprised 91 candidates – 70 females (mean age: 37.4 years, range: 16–67) and 21 males (mean age: 41.3 years, range: 6–86). Nonthyroiditis group had 154 candidates – 103 females (mean age: 43.2 years, range: 14–76) and 51 males (mean age: 39.9 years, range: 7–70). All patients in thyroiditis group were those with papillary thyroid cancer. 68/91 candidates with thyroiditis and 24/154 candidates without thyroiditis had positive ATA. The median ATA was 97.8 IU/ml (interquartile range [IQR] 246.2) and 16.7 IU/ml (IQR 15.48) for thyroiditis and nonthyroiditis groups, respectively, with this difference being statistically significant (P < 0.001). Positive ATA and occurrence of thyroiditis had a significant positive correlation (correlation coefficient 0.59, P <0.001) on Spearman's test. However, there was no significant difference between the age distribution among the groups, cumulative 131I dose, or time taken for the patients to become scan negative after receiving radioiodine therapy (P > 0.05). No patients in thyroiditis group developed TENIS while 8 patients developed TENIS in the nonthyroiditis group. Conclusion: The study shows that there is statistically significant positive correlation with elevated pre-131I-treatment thyroglobulin antibodies and occurrence of thyroiditis in the background of DTC. The higher levels of thyroglobulin antibodies interfere with usual assays for measurement of thyroglobulin levels. Hence, routine pre-131I-treatment measurement of thyroglobulin antibodies along with thyroglobulin has strong clinical significance in patients who has thyroiditis in the background of DTC.
| OP33: 68Ga-DOTA-RGD2 positron emission tomography/computed tomography in differentiated thyroid carcinoma patients with thyroglobulin elevation and negative 131I scintigraphy-stepping stone for novel theranostics | | |
Ashwin Singh Parihar, Bhagwant Rai Mittal, Rajender Kumar, Jaya Shukla, Rakhee Vatsa, Harmandeep Singh, Ashwani Sood, Anish Bhattacharya
Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Background and Objectives: Assessment of tracer uptake pattern on 68Ga-DOTA-RGD2 positron emission tomography/computed tomography (PET/CT) in differentiated thyroid carcinoma (DTC) patients with thyroglobulin elevation and negative 131I scintigraphy (TENIS) for determining suitable candidates for peptide-based radionuclide therapy. Materials and Methods: Twenty-one patients (mean age: 51.2 ± 10.7 years) of DTC with TENIS (rising stimulated serum thyroglobulin [S.Tg >10 ng/mL], negative anti-Tg antibodies and negative 131I whole-body scintigraphy) were enrolled in this prospective pilot study after voluntary, written, and informed consent. These patients underwent 68Ga-DOTA-RGD2PET/CT, on which semi-quantitative measurement of tracer uptake was done using SUVmax. Histopathologic correlation was performed wherever feasible. Correlation of S.Tg with number of tracer avid lesions and SUVmax was performed. Results: Median S.Tg was 241.2 ng/mL (range: 33–1278) at the time of the study. 18/21 patients had a minimum of one 68Ga-DOTA-RGD2 avid lesion with 12 patients having two or more tracer avid lesion sites (maximum 5). Mean SUVmax of the lesions was 6.8 ± 2.7 (least avid – cervical lymph nodes – SUVmax 2.4; highest avid –right femoral lesion – SUVmax 10.5). Tracer uptake in thyroid remnant was observed in 11/21 (mean SUVmax 6.4), lymph nodes in 14/21 (mean SUVmax 5.5), skeletal lesions in 8/21 (mean SUVmax 6.2), and lung nodules in 9/21 (mean SUVmax 4.4) patients. Histopathologic analysis in 11/21 patients was consistent with metastatic thyroid carcinoma. S.Tg had a statistically significant positive correlation with number of tracer avid lesions (r = 0.7, P = 0.002). S.Tg had a positive correlation with SUVmax (r = 0.2, P = 0.45). Age at diagnosis of TENIS syndrome had a negative correlation with the number of tracer avid sites (r = −0.16, P = 0.5). Three patients (mean S.Tg 37.6 ng/mL) who did not show any uptake on 68Ga-DOTA-RGD2 PET/CT did not have any structural abnormalities on CT. They were kept on follow-up with serial Tg values and ultrasound neck. Conclusion: This prospective study is the first to explore the utility of 68Ga-DOTA-RGD2 PET/CT in patients of DTC with TENIS. Due to limited effective treatment modalities for this group of patients, the need of the hour is to develop a precise, effective, targeted, and personalized molecular therapy with minimal adverse effects. As a pre-requisite to the peptide-based radionuclide therapy, this study explored the baseline RGD avidity of lesions in patients with surgically inaccessible lesions, who can be potential candidates for the RGD-based radionuclide therapy. With 18/21 (85.7%) patients having at least one tracer avid site (maximum: 5), there is significant potential for development and utility of RGD-based theranostics.
| PP32: Role of 99mtechnetium thyroid scan in assessment of cases of congenital hypothyroid-an institutional experience | | |
Madan Gopal Vishnoi, Braj Kishore Singh, Anurag Jain, K. P. Solanki, Arun Ravi John, A. G. Pandit
Army Hospital (Referral and Research), New Delhi, India
Background and Objective: Congenital hypothyroidism (CH) is the most common preventable causes of intellectual impairment and can cause irreversible neurodevelopment delay if not corrected with thyroxin replacement in infants. It has a worldwide annual incidence of 1:4000 live births. Incidence in India is not exactly known, but it varies from 1:500 to 1:3400 according to varies studies. Materials and Methods: A prospective observational study conducted at Army Hospital (R&R) over the period of 3 years from August 2015 to August 2018. The study comprises 13 children of diagnosed cases of CH who were subjected for Tc99m thyroid scan. All the patients underwent thyroid function test (TFT), ultrasonography (USG) neck, and Tc99m thyroid scan. Result of TFT, USG, and Tc99m thyroid scan was analyzed. Results: Thirteen children included in the study ranging from age of 28 days to 11 years. There are 6 female and 5 male children. TFT of all the children reveals low T4, T3, and high TSH level. Average TSH level is >10 μIU/ml. According to TFT, USG, and Tc99m thyroid scan result, children are divided in four groups.
- Group A: TFT – hypothyroid, USG neck – Normal thyroid gland in thyroid bed, Tc99m thyroid scan – no functional thyroid tissue in the thyroid bed or elsewhere in the scanned region, remark – likely due to dyshormonogenesis, iodine or drug interference
- Group B: TFT – hypothyroid, USG neck – no thyroid gland in the neck region, Tc99m thyroid scan – functional thyroid tissue at the base of tongue – likely lingual thyroid gland, Remark – Due to ectopic(lingual thyroid gland)
- Group C: TFT – hypothyroid, USG neck – no thyroid gland in the neck region, Tc99m thyroid scan – no functional thyroid tissue in the thyroid bed or elsewhere in the scanned region, Remark – likely thyroid agenesis
- Group D: TFT – hypothyroid, USG neck – normal thyroid gland in thyroid bed, Tc99m thyroid scan – functional thyroid tissue in the neck in the region of thyroid bed, Remark – normal trapping function but organification defect (e.g., Pendred's syndrome).
According to above results, thyroid imaging with technetium TC-99m provides information about the size, location, and functional status of the thyroid gland. Conclusion: Screening for CH should include USG neck and Tc thyroid scan along with TFT. Ultrasound neck is not an alternative for thyroid isotope scanning to define the etiology of CH.
| PP33: Prostate-specific membrane antigen expression in metastatic differentiated thyroid cancers using Ga-68 prostate-specific membrane antigen-HBED-CC positron emission tomography-computed tomography: A single-institution experience | | |
Vilas Meshram, GauravMalhotra, Priyanka Verma Soni, SunitaSonavane, Rahul V. Parghane, S. Rakshit, Ashok Chandak, Ramesh V. Asopa
Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Our study group showed utility of Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET-CT) in patients of metastatic thyroid cancer in a pilot study.[1] However, a study exploring PSMA uptake in larger population with varied presentations of advanced thyroid cancers is lacking. The aim of this study was to assess PSMA expression in the said patients of thyroid cancer. Materials and Methods: Thirty patients of metastatic differentiated thyroid carcinoma harboring 120 lesions (15 males; age range 29–79 years; mean age 57 years and 15 females, age range 22–67 years; mean age 51 years) underwent prospective evaluation with radioiodine (131I), 18F-labeled fluoro-2-deoxyglucose (18F-FDG) PET/CT, and 68Ga-PSMA-HBED-CC PET/CT scans as per the institution protocol. PSMA expression (SUVmax) was compared with 18F-FDG and 131I scan findings in all patients. Results: All the lesions were diagnosed to be associated with carcinoma of thyroid, based on functional imaging, CT correlation, fine-needle aspiration correlation (2 patients), and follow-up evaluation. These were radioiodine avid in 21 patients, whereas 9 patients were classified as thyroglobulin elevation with negative iodide scintigraphy (TENIS). All patients with iodine avid metastatic disease showed substantial PSMA uptake. PSMA PET/CT detected 95/120 lesions (79.16%), SUVmax ranging from 3.0 to 209.6 (median SUVmax: 22.08), whereas FDG PET/CT was positive in 109/120 lesions (90.83 %) (Average SUVmax: 12.42). PSMA expression was seen in 38 of 52 (73 %) soft tissue lesions while FDG uptake was seen in 48 of 52 (92.3%) soft tissue lesions. Both FDG and PSMA uptakes were seen in 63 of 68 (92.6%) bone lesions each. Nine patients of TENIS were harboring 14 soft tissue and 5 bone lesions. Seven of 9 TENIS patients (77.7%) showed FDG avid lesions, whereas PSMA avid lesions were seen in 6 patients (66%). FDG detected 13 of 14 soft tissue and all 5 bone lesions while PSMA detected 6 soft tissue and all 5 bone lesions, respectively. Conclusions: PSMA expression is seen in both iodine avid as well as TENIS cases. PSMA expression is more in bone lesions as compared to soft tissue lesions. It could be useful for patients with limited therapeutic options (e.g., TENIS) who might benefit from PSMA-targeted radionuclide therapy.
| PV27: Does technetium thyroid scintigraphy have a role in predicting remission in Graves's disease patients on antithyroid drugs? | | |
S. Padma, P. Shanmuga Sundaram
Department of Nuclear Medicine and Molecular Imaging, Amrita Institute of medical Sciences, Kochi, Kerala
Background and Objectives: Technetium thyroid scintigraphy (TcO4) is used in hyperthyroidism to establish the presence or absence of Graves's disease (GD) and decide on low-dose I-131 therapy. There are no data whether TcO4 thyroid scintigraphy can predict remission/relapse in GD patients on drug therapy. The study aims to establish if TcO4 scintigraphy has a role in predicting remission and relapse in documented GD patients on antithyroid medications (ATDs). Materials and Methods: Records of 174 patients who presented between January 2006 to 14 with (a) confirmed hyperthyroidism biochemically and scintigraphic evidence of GD, (b) remitters at least 1½ years postremission, (c) patients >12 years of age. Variables such as age, gender, smoking history, goiter, treatment duration, biochemical parameter, and dose of ATDs were analyzed. Time to normalization of thyroid function test was calculated along with time taken to reach the minimum dose of anti-thyroid drugs, remission, relapse at < 1 yr and after 1 yr, radioiodine treatment, presence of ophthalmopathy, dermopathy. Data compared between remission and nonremission groups. Mann–Whitney U-test and Chi-square tests used to compare the groups statistically. Results: 57/174 (32.7%) patients attained remission after at least 1 year of thionamides. 19.2% patients relapsed within 1 year. Age, gender, goiter, and extrathyroidal manifestations were not associated with remission. Time to achieving normal thyroid function and composite dose studied. Time scores were significantly associated with remission (P = 0.05 and P = 0.01, respectively). Patients with lower free T4 at presentation had higher chance of remission (P = 0.01). Those who remitted had faster normalization of thyroid function. Relapse rates were lower than previously reported in the literature. Patients with relapse (12.4% vs. 5.9%) had higher values of uptake (P = 0.009). Conclusion: This study clearly shows TcO4 thyroid scintigraphy is an additional factor in predicting remission as well as relapse in patients with GD. A lesser time taken for normalization of TFT has also been found to be positively associated with remission. Furthermore, the composite variable of the product of time taken for normalization of TFT and dose of ATD has emerged as a factor to predict remission. A lower value for the composite variable has shown a greater chance for remission prognostic factors associated with remission in GD in this study differing from that reported in Western literature and found to be lower. Thus, TcO4 thyroid scintigraphy serves to be a useful marker to predict outcome of GD in patients on ATD.
| PV28: Thyrotoxic periodic paralysis: A diagnostic and clinical challenge | | |
Amit Sharma, Yogesh Kumar, S. K. Agrawal, Neeraj
Command Hospital (Eastern Command), Kolkata, West Bengal, India
Background and Objectives: Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The aim of this article was to review the clinical presentation, pathogenesis, and management of TPP. We report case series of 10 patients of TPP. Materials and Methods: We report 10 consecutive patients in the last 5 years who reported to Command Hospital (Eastern Command), Kolkata. They were all men with median age of 31.5 years at presentation. They all presented with a paresis or flaccid paralysis, without respiratory failure. Previous similar episodes in their past medical history, the presence of hypokalemia, and the presence of clinical signs of hyperthyroidism led to the diagnosis of TPP. Results: Initially, all patients were treated with potassium supplementation, beta-blockers, and antithyroid drugs. Definite medical treatment was offered to all 10 patients. Eight patients were offered radioiodine therapy. Euthyroidism was achieved in four patients and hypothyroidism was achieved in rest six patients. There was no recurrence seen after definite therapy. Conclusion: TPP is a severe condition, due to a dysfunction of the Na(+)-K(+) ATPase pump. Initial management relies on beta-blocker treatment and careful potassium supplementation. Then, medical or surgical etiological treatment of the thyrotoxicosis is essential to prevent a recurrence. The disease is probably underdiagnosed: it must be suspected when a profound hypokalemia resolves very quickly (<12 h); hyperthyroidism should always be included in the differential diagnosis of a paresis associated with hypokalemia.
| PV29: I-131 clearance from patients undergoing radio iodine therapy for thyroid cancer | | |
T. M. Ginsha, H. K. Mohan, B. S. Srinath, B. Harish
Sri Shankara Cancer Hospital and Research Centre, Bengaluru, Karnataka, India
Background and Objectives: Radioactive iodine (I-131) is a standard-of-care treatment postsurgery in thyroid cancer patients. Following high-dose I-131 therapy, >30 mCi, patients are required by regulation, to be admitted in isolation rooms until the radioactivity levels fall to safe limits prior to discharging .The radio activity levels are monitored using Geiger counter (GM) held at 2 m distance from the patient. Once the dose rate levels fall below that expected for 30 mCi or less, the patients are discharged from the hospital. Currently, patients are admitted for 1–2 days following 100 mCi therapy and 2–3 days following >150 mCi administration. This study aims to find out the clearance of I-131 in patients admitted for I-131 ablation therapy (100 mCi) and for treatment of metastatic disease (>150 mCi). The information should help inform us of the minimum time required for patient isolation following I-131 therapy before their safe discharge back into the community. Materials and Methods: 40 patients were divided into two groups initially;
- Those undergoing therapy with 100 mCi (n = 21) and those undergoing >150 mCi (n = 19)
- Those with endogenous TSH stimulation (n = 36) and in those who were given recombinant TSH (n = 4) before I-131 therapy.
Clearance of radioactive iodine in all the groups were studied by evaluating the dose exposure rate measured sequentially using GM counter held at a distance of 2 m. The dose rates were measures at time intervals of 0 (immediately), 1, 4, and 24 h following I-131 administration. The average time to attain a safe exposure level was calculated for each subgroup. Results: All 21/21 patients treated with 100 mCi and 16/19 patients treated with 150 mCi reached dose rate levels safe for discharge back into community within 24 h of admission. Only 3 patients post >150 mCi administration needed to stay for >24 h (2 days) postadmission. Of the 36 with endogenous TSH stimulation, 91.67% (33 patients) reached safety level for I-131 within 24 h, and 8.33% (3 patients) reached safety level after 24 h. All 4 patients who were given recombinant TSH reached safety level well within 24 h. Conclusion: Following I-131 therapy, majority of the patients treated with 100 mCi and 150 mCi of I-131 and in those treated following rTSH stimulation can be planned to be safely discharged back into the community the following day. In a small proportion of patients treated with >150 mCi, the discharge will need to planned for after 24 h.
| PV30: Fictitious false-positive uptake in iodine-131 whole-body scan in patients with well-differentiated thyroid carcinoma: A case series | | |
S. A. Ashwin, Nandini Pandit, Dhanapathi Halanaik, Madhusudhanan Ponnusamy
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background: The whole-body (WB) iodine-131 scan is routinely performed in postoperative treatment of patients with well-differentiated thyroid cancer. It represents the important tool to detect remnant tissue as well metastases to lymph node/distant sites. Unfortunately, false-positive uptake in several other organs has been reported. Case Summary: (1) A 28-year-old female case of papillary thyroid carcinoma underwent total thyroidectomy. Diagnostic WB iodine scan done with administration of 2 mCi of I-131 orally revealed significant remnant in thyroid bed with submandibular gland enlarged. She received 30 mCi of I-131. Posttherapy scan revealed situs inversus with remnant in thyroid bed. Mildly increased tracer was noticed in lung fields close to mediastinum. High-resolution computed tomography (CT) thorax showed cystic bronchiectasis changes in inferior segment of lingula on right and medical lateral segment of middle lobe of left side. (2) A 23-year-old female case of papillary thyroid carcinoma underwent total thyroidectomy. Diagnostic WB iodine was scan with 2 mCi of I-131 revealed significant remnant in thyroid bed. Abnormally increased focus of increased uptake seen in right side of pelvis, single-photon emission CT (SPECT)/CT of the pelvis showed increased uptake in a cystic lesion with areas of hypodensity in right adnexa (right ovary). She underwent surgical exploration and complete excision of cystic mass. Biopsy was suggestive of mature cystic teratoma. (3) A 34-year-old female case of follicular thyroid carcinoma underwent total thyroidectomy. WB diagnostic scan with 3 mCi showed remnant in thyroid bed with L5 vertebral metastases. She received 95 mCi of I-131 therapy. First follow scan showed no residual tissue in neck with mild increased uptake in L5 vertebrae. She received 250 mCi of I-131 therapy. Posttherapy scan revealed abnormally tracer in left upper ribs posteriorly, L5 vertebrae, and faint uptake in the pelvis region. SPECT/CT of pelvis shows uptake corresponding to uterus region. (4) A 23-year-old case of papillary carcinoma thyroid underwent total thyroidectomy. Diagnostic WB scan done with administration of 3 mCi of I-131 showed remnant in thyroid bed and thyroglossal tract with no evidence of distant metastases. She received 150 mCi of I-131. Posttherapy scan revealed remnant in thyroid bed with abnormal uptake in upper mediastinum. SPECT/CT of the thorax showed uptake corresponding to enlarged thymus. Conclusion: Post I-131 scan enables identification of ectopic uptake and staging of patients and should be interpreted on basis of clinical, serum thyroglobulin, and other parameters. False-positive uptake is not uncommon and their recognition is important to prevent costly additional therapy.
| PV31: Can postoperative serum thyroglobulin alone drive decisions on I-131 therapy in patients with differentiated thyroid cancer? | | |
Shankaramurthy Gayana
New Medd Diagnostics, Bengaluru, Karnataka, India
Background and Objectives: In clinical thyroidology, recent trend is to de-escalate the role of I-131 therapy in early differentiated thyroid cancer (DTC). Although serum thyroglobulin (Tg) levels provide valuable information of achieving remission or having recurrent disease following I-131 therapy, the role of postoperative serum Tg alone as a criterion to judge whether a patient requires adjuvant I-131 therapy or not is debatable. The purpose of this study was to assess the diagnostic accuracy of serum Tg as compared to LD scan in driving I-131 therapy in patients with early stages of DTC. Materials and Methods: We studied 191 patients with low and intermediate pathological risk of DTC, out of which 135 (71%) were females and 55 (29%) were males, with mean age group of 40.9 years. 127 (66%) were below the age of 45 years and 64 (34%) were above 45. LD scan was done after 24 h of administration of 3 mCi of I-131 using dual-head single-photon emission computed tomography (SPECT) system and SPECT/CT was done in selected cases. Serum Tg assay was done in all patients using CLIA method. Mean interval of scan was 39 days postsurgery and mean TSH was 92.3 μIU/ml. Results: Out of 193 patients, 27 patients had small remnant, 60 significant remnant, 93 cervical lymph nodes, 8 cervical + mediastinal nodes, and 3 lung metastasis. 29 (15%), 81 (42%), and 95 (49%) patients with Tg levels <2 ng/ml, <5 ng/ml, and 10 ng/ml had lymph nodal metastasis on LD scan. Two patients with Tg levels of 0.6 ng/ml and 1.2 ng/ml had lung metastases. Furthermore, 27 (14%) patients with Tg values of >100 ng/ml had only regional lymph nodal metastases, without any visceral or skeletal metastases. Based on LD scan findings, dose of I-131 administered was increased in 49% of patients. Conclusion: Deciding on I-131 therapy based on postoperative serum Tg alone will be inappropriate and cannot be safely avoided even in patients with serum Tg <2 ng/ml. LD scan changed management in 42% of cases. It also influenced the administered I-131 dose compared to serum Tg alone. Any metastatic recurrence in DTC is unacceptable, and therefore, LD scan followed by I-131 therapy needs to be the standard management, even in low-grade DTC. Although serum Tg has prognostic significance, it cannot alone guide I-131 therapy even in patient with Stage I and II DTC.
| PV32: Correlation between clinical and scintigraphic findings in pediatric hypothyroidism | | |
Meivel Angamuthu, Nishikant Damle, Shreya Datta Gupta, Geetanjali Arora, Meghana Prabhu, Chandrasekhar Bal, Madhavi Tripathi, Avinash Tupalli, Rajni Sharma, Vandana Jain
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: Thyroid scintigraphy is performed in the pediatric population as a part of evaluation for congenital hypothyroidism, to look for ectopic thyroid tissue, or sometimes in the evaluation of thyrotoxicosis. Materials and Methods: We did a retrospective analysis of Tc-99m pertechnetate thyroid scintigraphies performed in our institute between January 2017 and June 2018 in the pediatric age group (≤18 years). Various parameters such as age, sex, clinical presentation of the child and referral pattern for thyroid scan, thyrotropin levels, and scintigraphic findings were reviewed. A total of 66 Tc-99m pertechnetate thyroid scans were performed in the pediatric population during the above-mentioned period. Among these, thyrotropin values could not be retrieved for 11 cases. Therefore, 55 children who underwent thyroid scintigraphy were included for analysis. Results: Among the children referred for thyroid scan, 29 were male and 26 were female. Median age was 6.25 years (interquartile range 2, 10.25). Based on thyrotropin values, 31 were hypothyroid, 9 were hyperthyroid, and 15 were euthyroid. The most common clinical condition for which thyroid scan was performed was hypothyroidism (21), including congenital hypothyroidism (15) and late-onset subclinical or overt hypothyroidism (6). The other referral conditions in our group were thyroid nodule (11) including suspected autonomously functioning thyroid nodule (2), thyrotoxicosis (4), goiter under evaluation (3) including painful goiter (1), syndromic associations (7) (including Down's, Goldenhar's, and William's syndrome), thyroglossal cyst (5), suspected ectopic thyroid tissue (2), and posthemithyroidectomy (1) to confirm extent of surgery. Thyroid scintigraphy findings were analyzed and correlated with referred clinical indication and thyrotropin values. Among 55 cases, thyroid scan findings corroborated exactly with clinical diagnosis in 22 cases but contradicted the clinical impression in 2 cases. Thyroid scan added further information to clinical diagnosis, though that would not have had much impact in the management, in 24 children. Thyroid scan was found to have no utility in 7 cases. Conclusion: Thyroid scan is a simple investigation that helps clinician to establish early and correct diagnosis. Clinical referrals are seen for conventional as well as unconventional indications. Tc-99m pertechnetate scintigraphy appears to have a supportive role in confirmation or modification of clinical diagnosis.
| PV33: Papillary carcinoma of thyroid in the background of hyperthyroidism: A case series | | |
Kota Keerthi Chandra, Nandini Pandit, Dhanapathi Halanaik, Madhusudhanan Ponnusamy, Gowri Sankar
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Objectives: Coexistence of hyperthyroidism and thyroid cancer is rare. Hyperthyroidism can be of diffuse toxic goiter (DTG), toxic multinodular goiter, or autonomously functioning thyroid nodule. In this study, we report a series of cases having hyperthyroidism with coexisting papillary carcinoma of thyroid. Materials and Methods: In this study, we observed six adult cases of who presented with anterior neck swelling and thyrotoxic symptoms. Biochemically, they were hyperthyroid and they underwent thyroid scan as a part of patient clinical workup. Thyroid scan was acquired after administration of 5 mCi of Tc-99m pertechnetate. Spot images of the neck and mediastinum in anterior and anterior oblique were acquired after 20 min. Out of 6 cases, two cases have hypofunctioning nodules in the background of DTG. They later underwent ultrasonography (USG)-guided fine-needle aspiration cytology (FNAC) which was highly suspicious for malignancy. They underwent total thyroidectomy with central compartmental lymph nodal dissection. Postoperative biopsy turned out to be papillary carcinoma of thyroid in these cases. Thyroid scan of 3 cases showed autonomously functioning thyroid nodule (AFTN), and they were planned for radio iodine ablation. Before giving therapy, they underwent screening USG neck where we found suspicious hypoechoic nodule. FNAC from the nodules showed Bethesda category V and VI lesions. One case was lost to follow-up. Two cases underwent total thyroidectomy along with central compartmental lymph nodal dissection. Postoperative biopsy was reported as papillary carcinoma, classical variant. Out of 6 cases, thyroid scan of one scan showed DTG with no hypofunctioning areas. As the swelling was extending almost up to sternal notch, CT scan of the neck was done which showed tracheal compression. In view of tracheal compression, the patient underwent total thyroidectomy and postoperative biopsy came out as multifocal papillary carcinoma. Results: Out of 6 hyperthyroid (both clinically and biochemically) cases reported, two had DTG with hypofunctioning nodules, 3 had AFTN, and 1 had DTG. Histopathologically, all these patients had papillary carcinoma of thyroid. According to the literature, carcinomas found in most of the AFTNs are either follicular carcinoma or follicular variant of papillary carcinoma. Here, we have classical variant of papillary carcinoma along with AFTN which is rare presentation. Conclusion: Thyroid carcinoma in hyperthyroidism will alter the patient management. Doing USG neck before radioiodine therapy will be useful.
| PV34: Clinical utility of 18F fluoro-deoxy-glucose positron emission tomography-computed tomography concurrent with 131I therapy in intermediate or high-risk differentiated thyroid cancer | | |
Malasani Vindhya, Ishita B. Sen, Vineet Pant, Parul Thakral, Sugandha Dureja, U. N. Pallavi, Kanchan Sharma
Department of Nuclear Medicine, Fortis Hospital, Gurgaon, Haryana, India
Background and Objectives: Early detection of iodine-negative differentiated thyroid cancer (DTC) lesions is important because it triggers an adjustment in the treatment strategies. The uptake of fluoro-2-deoxyglucose (FDG) has been considered as a surrogate marker of potential iodine refraction and more aggressive behaviors of DTC. This study was aimed at establishing whether performing an FDG positron emission tomography-computed tomography (PET CT) scan as a routine in patients with intermediate- or high-risk DTC helps identify a subset of patients who would not respond to radioiodine therapy. The study aims to determine incremental value of 18F-FDG PET CT in postoperative risk stratification of patients with intermediate- to high-risk DTC over pathological staging, postoperative whole-body scan (WBS), and postoperative serum thyroglobulin and to determine whether the patients with FDG avid residual or metastatic disease had a different clinical course compared to those who had non-FDG avid disease. Materials and Methods: Fifty postoperative patients with intermediate- to high-risk DTCs according to the ATA risk stratification were included in this study. All patients underwent thyroxine withdrawal for 3 weeks before evaluation with a serum thyroid-stimulating hormone levels greater than 30 uIU/ml at the time of evaluation. Serum Tg, anti-Tg, diagnostic whole-body iodine scan, and 18F-FDG PET CT scans were performed according to the standard protocol. The therapeutic 131-I dose was decided according to the patient's risk of structural recurrence. Posttherapy whole-body 131-I scans were performed between 3 and 7 days after 131-I treatment. All these patients were followed up for 6 months, with stimulated serum Tg and anti-Tg levels, diagnostic low-dose 131-I-WBS, and 18F-FDG PET CT scans. Results: Of the 50 DTC patients, the residual or metastatic disease was detected in the low-dose 131-I WBS in 41/50 patients and 18F-FDG scan could detect it in 22/40 patients. Concordance between the two scans was found in 13/50 patients. Of these 22 18F-FDG-positive patients, nine did not show iodine uptake. In three of these nine patients, there was evidence of residual gross disease and patients underwent resurgery, followed by radioiodine (RAI) therapy based on their initial risk stratification. At 6-month follow-up, all the three patients with FDG avid disease who underwent resection were found to be disease free. In the other six patients, who were given empiric RAI therapy despite negative diagnostic scan, 4/6 showed evidence of progressive disease. The other two patients demonstrated persistent stable residual disease.
| PV35: Preablation 131-I scan with single photon emission computed tomography/computed tomography in differentiated thyroid cancer: Impact on postoperative staging and risk stratification | | |
Swati Rachh1,2, Natasha Singh1, Melvika Pereira1, Amit Abhyankar1
1Department of Nuclear Medicine, P. D. Hinduja National Hospital and MRC, Mahim, Mumbai, Maharashtra, 2Department of Nuclear Medicine, The Gujarat Cancer and Research Institute, M. P. Shah Cancer Hospital, Ahmedabad, India
Background and Objectives: To determine the contribution of preablation whole-body iodine 131 (131-I) planar and single photon emission computed tomography/computed tomography(SPECT/CT) diagnostic scans for postoperative staging and risk stratification in patients with differentiated thyroid cancer (DTC). Materials and Methods: A total of 68 patients with DTC, posttotal thyroidectomy, were initially staged based on clinical and pathology data (pTN) and then restaged after imaging using American Joint Committee on Cancer (AJCC) tumor, node metastasis (TNM) staging, seventh edition. The impact of 131-I whole-body scan (WBS) with SPECT/CT was assessed in younger age group <45 years (n = 34) and older age group >45 years (n = 34), with subgroup analysis for T1a and T1b tumors. Initial risk stratification was performed using clinical and histopathological information. The risk stratification re-performed after consideration of preablation 131-I WBS and stimulated thyroglobulin (Tg) information. Results: In younger patients, 131-I WBS detected distant metastases in 3 of 34 (9%) patients and nodal metastases in 14 of 34 (42%), patients including unsuspected nodal metastases in 10 of 25 (40%) patients initially assigned pathological pN0 or pNx. In older patients, distant metastases were detected in 4 of 34 patients (12%) and nodal metastases in 11 of 34 patients (32%) including unsuspected nodal metastases in 9 of 29 (31%) patients initially assigned pN0 or pNx. 131-I WBS detected distant metastases in 1 of 9 (11%) T1a and 2 of 9(22%) T1b patients. Detection of unsuspected nodal and distant metastases and elevated stimulated Tg levels resulted in change in the estimated risk of recurrence in 18% of patients as compared to initial risk stratification based on postoperative neck histopathology alone. Conclusion: 131-I WBS detected regional metastases in 38% of patients and distant metastases in 10% of patients changing staging in 4% of younger and 7% of older patients, hence further changing risk stratification in 18% of patients as compared to recurrence risk estimation based on histopathology alone.
| Miscellaneous Track | | |
| OP34: Relation between duration of sicca symptoms and quantification parameters in salivary scintigraphy: A retrospective cross-sectional observational study | | |
Kota Keerthi Chandra, Dhanapathi Halanaik, Nandini Pandit, Madhusudhanan Ponnusamy
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Objectives: Salivary scintigraphy is a useful study in the functional assessment of major salivary glands. There are multiple quantification parameters which were proposed by different authors. In this study, we assessed the quantification parameters and observed their relation with the symptom duration. We designed a study to observe the relation between the duration of sicca symptoms and the salivary scintigraphy quantification parameters. Materials and Methods: This is a retrospective cross-sectional observational study. Patients who were referred for salivary scintigraphy and having sicca symptoms in between February 2018 and July 2018 were included in the study. Quantification parameters were assessed separately for all the four major salivary glands in the form of excretion fraction (EF %), secretion velocity (SV %), and maximum accumulation at 15th min (MA15%). EF % (maximum counts prestimulation − minimum counts poststimulation/maximum counts prestimulation), SV % (maximum counts at 15th min − minimum activity at 16th min/maximum counts at 15th min), and MA15% (maximum counts at 15th min − minimum activity at 1st min/maximum counts at 15th min) were calculate according to the defined formulae. Total (N = 48) scans were divided into three groups depending on the duration of symptoms in as 1–2 months (n = 19), 3–12 months (n = 20), >12 months (n = 9). The comparison of means of all parameters was made by one-way ANOVA test. Results: There was statistically significant difference (P < 0.05) between the groups in 4 out of 12 parameters that were analyzed, but the relationship was not a linear manner. Conclusion: There was no relationship between duration of sicca symptoms and quantification parameters in salivary scintigraphy.
| OP35: 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography: A valuable tool for initial evaluation and therapeutic response assessment in patients diagnosed with relapsing polychondritis | | |
Apurva Sood, Rajender Kumar, Aman Sharma1, Sanjay Jain1, Ashwin Singh Parihar, Anish Bhattacharya, Bhagwant Rai Mittal
Departments of Nuclear Medicine and 1Internal Medicine, PGIMER, Chandigarh, India
Background and Objectives: Relapsing polychondritis (RPC) is a rare immune-mediated condition of unknown etiology, associated with recurrent inflammation of the cartilage throughout the body. Varied clinical features and course of RPC make the diagnosis and assessment of therapy response challenging. 18F-labeled fluoro-2-deoxyglucose (F18-FDG) has growing importance in the field of inflammatory and infectious diseases but still does not have a well-established role in RPC. The objective of this retrospective study is to investigate the role of F18-FDG positron emission tomography-computed tomography (PET/CT) for initial evaluation and therapeutic response assessment in patients diagnosed with RPC. Materials and Methods: Cases of RPC diagnosed on the basis of Damiani and Levine modification of McAdam criteria who underwent F18-FDG PET/CT at baseline and one during or following therapy were evaluated. Visual and semi-quantitative (SUVmax) analysis of PET imaging was done. The response to therapy was characterized as follows: decrease in the number and uptake in the involved cartilages (favorable response [FR]; no uptake (complete metabolic response [CMR]); appearance of new lesions or increase in the SUVmax of the lesions (progressive disease [PD]), and neither FR nor PD (stable disease [SD]). PET findings and clinical course of the disease were correlated. Results: A total of 9 patients (male:female = 3:6; age:21–46 years) were evaluated. The initial PET/CT scan was positive in all nine patients. Of these, five patients had more than two cartilage involvement while four patients had only one cartilage involvement. F18-FDG avid thickening was noted in nasal cartilage (n = 5), ear cartilage (n = 3), Eustachian tube (n = 1), cricoid cartilage (n = 2), thyroid cartilage (n = 1), arytenoids (n = 1), tracheal/bronchial cartilage (n = 4) and arch of aorta (n = 1). 18F-FDG PET detected bronchial involvement in two asymptomatic patients and thyroid cartilage and Eustachian tube involvement in one each. Six patients underwent follow-up scan during steroid therapy, at an interval ranging from 2 to 9 months. CMR, FR, and SD was seen in three (absent uptake vs. SUVmax 6.2 ± 1.3), two (SUVmax 1.6 ± 0.35 vs. 3.8 ± 1.9) and one (SUVmax 1.9 vs. 1.6) patient, respectively. Three cases underwent scan following completion of therapy and showed CMR in one (SUVmax 2.3 vs. 0.4) and PD in two (SUVmax 2.7 ± 0.85 vs. 4.75 ± 0.25) patients. Cases with CMR and FR showed clinical improvement while the cases with SD and PD were started on additional medications. Conclusion: F18-FDG PET/CT not only helped in early identification of clinically asymptomatic life-threatening bronchial involvement in this chameleon disease but also assisted in recognizing lesions in clinically uninvolved sites. Furthermore, PET/CT also aids in therapy response assessment.
| OP36: Fungal infection imaging using Tc-99m-labeled voriconazole | | |
Kanchan Palarwal, Rakhee Vatsa, Priya Bhusari, Anupriya Chhabra, Bhagwant Rai Mittal, Jaya Shukla
Department of Nuclear Medicine and PET, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Background and Objectives: Fungal infection poses a serious threat to individuals who are immune compromised. The invasive techniques histopathology and culture still remain the gold standard for fungal infection detection. Voriconazole, a triazole, exhibits antifungal action by impairing the production of ergosterol in the fugal cell membrane. The present study aims to radiolabel voriconazole with Tc-99m for noninvasive imaging of fungal infection. Materials and Methods: Tc-99m was used to radiolabel commercially available voriconazole via stannous reduction method. The reaction volume was restricted to 1 ml. The pH of reaction mixture was varied from 2 to 8 with incubation at room temperature for 5–25 min. Quality control was performed using saline and acetone as mobile phase. In vitro uptake studies were performed in Escherichia coli and Candida albicans along with Ascaris fumigatus strain. Radioactivity was measured in supernatant and pellet. Results: Greater than 98% radiolabeling yield was achieved by incubating 5 mCi of Tc-99m with 100 μg of voriconazole at 3.5–4.0 pH for 15–20 min at room temperature. Radiochemical purity of ~100% was achieved as observed in radio-ITLC. Rf in saline and acetone was observed 0.7–0.8 and 0.0, respectively. No uptake in bacterial cells and around uptake is seen in fungus. Conclusion: Voriconazole was successfully labeled with Tc-99m and is specific for fungal cell as observed in in vitro study. However, further in vitro studies need to be done to establish the role of Tc-99m voriconazole as a potential radiopharmaceutical for noninvasive imaging of fungal infections.
| PP34: Visualization of pulmonary hemorrhage in patients of anti-glomerular basement membrane syndrome using 99mTc RBC scintigraphy, single-institute experience | | |
Praveen Lolla
Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
Background and Objectives: Pulmonary hemorrhage is generally due to neoplasm, tuberculosis, necrotizing pneumonia, or bronchiectasis. If these are not detected, renal disorders including anti-glomerular basement membrane (GBM) antibody-induced bleeding (Good pasture's syndrome) should be considered. Radiolabeled study is a noninvasive measure of pulmonary hemorrhage in patients of anti-GBM syndrome. It provides clinically useful information regarding the site of bleeding that is not available from medical history, physical examination, or chest X-ray. Materials and Methods: 99mTc-labeled RBC scintigraphy is performed in seven patients of suspected anti-GBM syndrome from May 2016 to May 2017 throughout 1 year in the Department of Nuclear Medicine, SVIMS, Tirupathi. By in vivo method, all the patients are injected with bolus of 15–30 mCi of 99mTc RBC and rapid image acquisition at a rate of 1 frame per 2 s for duration of 60 s is performed. Dynamic images are acquired in 10–15 min sequence throughout 60 min. Delayed imaging for 24 h is not done in any patients. Results: Of the 7 patients, five patients are diagnosed with pulmonary hemorrhage on 99mTc RBC scintigraphy. There is no evidence of pulmonary hemorrhage in two patients. Conclusion: 99mTc RBC scintigraphy is an effective, noninvasive imaging modality and can provide complimentary information in the evaluation of anti-GBM disease. Use of this modality in correlation with other investigations helps in early diagnosis of disease, thus improving patients' outcome.
| PP35: Role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in determining the disease burden and its impact on intervention in tubercular lymphadenitis | | |
Kasturi Rangan, Sanjay Gambhir, Survesh Kumar1, Nikhil Kakani1, Ajay S. Suraj, Mudalsha Ravina
Departments of Nuclear Medicine and 1General Surgery, SGPGIMS, Lucknow, Uttar Pradesh, India
Background and Objectives: Tubercular lymphadenitis though can present as localized disease but most of the time multiple groups of lymph nodes involved. We explored the role of whole-body 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) to determine the disease burden, its correlation with response to treatment, and possibly duration of treatment. Materials and Methods: Thirty patients with pathologically proven tubercular lymphadenitis were subjected to pretreatment whole-body 18F FDG PET/CT scan and subsequent post-antitubercular treatment (ATT), PET/CT scans were done at 2 and 6 months. Based on the metabolic response to the treatment, scans were categorized into complete metabolic response (CR), partial metabolic response (PR), stable disease (SD), and progressive disease (PD). CR was defined as complete disappearance of metabolic activity while PR as disappearance of activity in some of the nodes or >30% reduction in the SUVmax. SD in case of no significant change from the baseline and PD in appearance of new lesion or >30% increase in the SUVmax. Results: Among 30 patients, the median age was 39 (range, 18–66) years and male:female was 1.3:1. Apart from palpable cervical lymph nodes, whole-body 18F FDG PET/CT revealed additional cervical lymph nodes in all patients (average SUVmax – 5.4, size – 16 mm), 12 patients with mediastinal lymph nodes(average SUVmax – 4.5, size – 18 mm), 8 patients with abdominal lymph nodes (average SUVmax – 3.98, size – 15 mm). Overlapping of these regions was often seen, of which all the three compartmental involvements were noted in 6 patients, cervicomediastinal region in 5 patients, and mediastinal-abdominal regions in 6 patients. Additional findings such as Potts spine, lung involvement, liver to splenic reversal, bone marrow activation, and psoas abscess were noted. Follow-up was done after second month of starting ATT in 24 patients and 6 months of ATT in 8 out of 24 patients. After 2 months of ATT, 2 patients had CR, 20 had PR, and 2 had progression. After 6 months of ATT, 1 patient had CR, 5 PR, and 2 PD. Conclusions: 18-F-FDG-PET/CT has excellent clinical role in eliciting of actual disease burden in systemic tubercular lymphadenitis. At 6 months, most of the lymph nodes responded partially to the treatment with evidence of remnant disease, thus indicating need for completing the extended course of ATT.
Acknowledgment: We would like to acknowledge IAEA, CRP E 15021.
| PP36: Comparison of Tc-99m phytate with Tc-99m sulfur colloid in patients with bilateral/unilateral lower limb lymphedema using lymphoscintigraphic scan | | |
Jyoti Mishra
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Objectives: Lymphoscintigraphy helps evaluate our body's lymphatic system for abnormalities using small amounts of radioactive materials called radiotracers that are typically injected into the skin via subcutaneous or intradermal route. It has emerged as the diagnostic study of choice to evaluate for the presence of lymphedema. Lymphoscintigraphy is usually done with Tc-99m sulfur colloid (SC), which has limitations such as tedious method of preparation, high amount of initial activity required, and a range of particle size even after filtration. However, Tc-99m phytate is also used for lymphoscintigraphy, requires less activity for preparation, and is also easier to prepare. This study is aimed at comparing the effectiveness of Tc-99m phytate with that of Tc-99m SC. The study aims to compare lymphoscintigraphy scans done in patients with bilateral/unilateral lower limb lymphedema using Tc-99m SC and Tc-99m phytate. Materials and Methods: This study was carried out retrospectively in 30 lymphoscintigraphy scans (18 scans using Tc-99m SC and 12 scans using Tc-99m phytate). Tc-99m SC or Tc-99m phytate was injected as 0.5 mCi each in the first web space of bilateral feet subcutaneously. Scan was acquired as sweep images covering upper abdomen to the feet, in 256 × 1024 matrix. All the scans were acquired immediately after injection, postexercise, and delayed after 2 and 4 h. Results: A total of 30 lymphoscintigraphy scans were included for analysis. For both the radiopharmaceuticals, it was found that while postinjection images showed superficial lymphatics and the injection site, postexercise images showed superficial lymphatics, inguinal lymph nodes, and/or popliteal lymph nodes. Delayed images revealed inguinal and iliac group of lymph nodes in both groups. Conclusion: Lymphoscintigraphy with Tc-99m phytate has the advantages of being technically easier compared to imaging using Tc-99m SC while being qualitatively similar.
| PV36: Role of 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography in prospective and postlung-transplant recipients | | |
S. D. Abdul Rahim, Shelley Simon, M. Indirani
Department of Nuclear medicine, Apollo Hospital, Chennai, Tamil Nadu, India
Background and Objectives: Selection of patients for lung transplantation poses a few challenges, malignancy within 2 years is one of them, it is an absolute contraindication for lung transplantation, as the risk of lung cancer in prospective lung-transplant recipients is similar to that of high-risk population (1%–2%) for pulmonary malignancy, and it becomes essential to rule out the possibility of malignancy. Since 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography (F-18 FDG PET/CT) has high negative predictive value for malignancy, it is a well-suited investigation to rule out malignancy. In context of postlung-transplant recipient's detection of new nodules, mass, progressing lymphadenopathy, posttransplant lymphoproliferative disorder, primary lung malignancy, or atypical infection is of important concern. F-18 FDG PET/CT is an effective tool for the detection of disease and to designate an appropriate site for tissue sampling in the above scenario. The study aims to evaluate the role of PET/CT in prospective and postlung-transplant recipients. Materials and Methods: It is a study comprising 10 patients, 8 were prospective lung-transplant recipients and 2 were postlung-transplant recipients; all them had underwent F-18 FDG PET/CT. Results: In the all prospective recipient's with interstitial lung disease, no malignancy was detected. In postlung-transplant recipients, granulomatous disease was identified in one recipient and bronchiolitis obliterans syndrome in the other. In our study, all the prospective transplant recipients were negative for malignancy, F-18 FDG PET/CT is highly sensitive for identification of malignancy, but it is not specific, so if any suspicious nodules detected should be worked up further with histopathology correlation. Posttransplant recipient with granulomatous disease was worked up further and appropriate treatment was given. Conclusion: F-18 FDG PET/CT serves as the one-stop noninvasive imaging modality in both prospective and postlung-transplant recipients.
| PV37: Hepatopulmonary syndrome demonstrated by Tc-99m macroaggregated albumin whole-body scintigraphy: A rare | | |
S. A. Ashwin, Nandini Pandit, Dhanapathi Halanaik, Madhusudhanan Ponnusamy
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background: Hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, pulmonary gas exchange abnormality leading to arterial deoxygenation and evidence of intrapulmonary vascular dilatation. The prevalence in the setting of cirrhosis varies from 4% to 47%. This disparity in prevalence rates can be due to different cutoff in defining arterial hypoxemia. Case Summary: A 65-year-old male patient presented to surgical gastroenterology outpatient department with a history of abdominal distension, bilateral leg swelling for 6 months; history of dyspnea on exertion of NYHA grade 4 for 4 months; known chronic liver disease for 8 years on conservative management and known alcoholic for 30 years. On examination, the patient was well oriented, icterus ++, pallor ++++, clubbing grade 3, bilateral pitting edema till knee joint. The patient had persistent hypoxemia (pO2 <80%) despite oxygen supplementation. Investigations revealed total bilirubin – 2.34 mg/dl, direct bilirubin – 3.71 mg/dl, and prothrombin time – 20.2 s. Rest of the blood parameters were within normal range. In suspicious of HPS, contrast-enhanced echocardiography was done which was suggestive of extracardiac shunt. Then, the patient was subjected to Tc-99m MAA whole-body scintigraphy which again was suggestive of shunting of blood. Results: Image finding of Tc-99m MAA whole-body scintigraphy – the whole-body images showed activity in intestine, spleen, kidney, and brain in addition to normal lung activity. Diffuse soft tissue uptake labeling the whole body was also noted. These findings were consistent with right to left shunt. The shunt fraction was calculated (total body counts − total lung counts/total body counts) which came to be ~20%, which confirmed the right-to-left shunt. Pathophysiology – the pathogens is of HPS remains unknown. The hallmark of HPS is microvascular dilatation within the pulmonary arterial circulation. Microvascular dilatation impairs ventilation perfusion matching and can produce anatomical and functional shunt physiology, leading to hypoxemia. The inadequate synthesis or metabolism of the pulmonary vasoactive substance by damaged liver is believed to be reason for functional vasodilation of the pulmonary vasculature (i.e., imbalance between vasoconstrictor and vasodilator substances). Diagnosis – right-to-left shunt associated with pulmonary vascular vasodilation secondary to HPS. Conclusion: Right-to left shunt due to pulmonary vasodilation is manifestation of HPS. Although contrast-enhanced echocardiography is considered gold standard, Tc-99m MAA imaging can confirm right-to-left shunt noninvasively.
| PV38: Pictorial essay of various rare nononcological indication of diagnostic nuclear medicine: An institutional experience | | |
Surekha Yadav
Army Hospital (Research and Referral), New Delhi, India
Background and Objectives: This presentation focuses on the potential of advanced applications of functional molecular imaging in assessing tumor biology and cellular characteristics with emphasis on positron emission tomography (PET) applications with both 18-fluorodeoxyglucose (FDG) and non-FDG tracers. Rare cases from various disciplines of medicine are discussed to find out the Roe Go diagnostic nuclear medicine outside of oncology. Discussion: few cases in the pictorial essay are (1) neurological – Moyamoya disease, Rasmussen encephalitis, progressive supranuclear palsy and MSA-P; (2) cardiological – infective endocarditis and cardiac sarcoidosis; (3) vascular surgery – femoropopliteal graft infection; (4) endocrinology – parathyroid adenoma, congenital hypothyroidism; and (5) Miscellaneous – Castleman's disease, stiff person syndrome, and paraneoplastic syndromes. Conclusion: 18F-FDG PET CT and other radiotracers can provide high yield in localization of hidden infection and pathophysiology in body and reduce the morbidity and mortality in affected patients. The cases are discussed in view of the PET-CT findings and the available literature.
| Radiation Safety Track | | |
| OP37: Impact of low tube voltage and low contrast volume on image quality, radiation dose, and biological effects at 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography studies | | |
Amit Nautiyal, Tanmoy Mondal1, Aruna Kaushik2, Deepanjan Mitra, Harish Chandra Goel3, Alpana Goel4, Subrata Kumar Dey1, Anirban Mukherjee, Piyali Chatterjee, Anindya Roy
Institute of Nuclear Medicine and Molecular Imaging, AMRI Hospitals, Dhakuria, 1Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, Salt Lake, Kolkata, 2Institute of Nuclear Medicine and Allied Sciences, S. K. Mazumdar Marg, Timarpur, Delhi, 3Amity Center for Radiation Biology, Amity University, 4Amity Institute of Nuclear Science and Technology, Amity University, Noida, Uttar Pradesh, India
Background and Objectives: Contrast-enhanced 18F-labeled fluoro-2-deoxyglucose (18F-FDG) whole-body positron emission tomography-computed tomography (WB PET/CT) investigations involve injection of contrast media having high atomic number iodine atoms that may enhance DNA damage at diagnostic energies. The objective of this study was to compare image quality, radiation dose received, and associated biological effects for weight adjusted contrast enhanced and reduced tube voltage scan protocol with the standard WB PET/CT protocol. Materials and Methods: The study was approved by the institutional ethics committee. Sixteen oncology patients who had previously undergone WB PET/CT examination at our institution using fixed omnipaque contrast dose (90 ml), standard 120 kVp tube voltage, and 18F-FDG injection (10.12 ± 0.23 mCi) were prospectively imaged using a weight-adjusted 300 mgI/mL omnipaque contrast dose (54.25 ± 8.39 ml), reduced 100 kVp tube voltage, and 18F-FDG injection (10.09 ± 0.24 mCi). For quantitative, image quality assessment, image noise, signal-to-noise ratio, contrast-to-noise ratio, and uniformity were measured in liver and paravertebral muscle for CT. Coefficient of variation and maximum-to-background ratio in the liver and aorta for PET. Qualitative assessment was performed by two nuclear medicine physicians and one radiologist, using 30-point grading score (>25 = excellent, 20–25 = good, 15–20 = average, and <20 = not reportable). Phantom study was also performed for the assessment of image quality. Radiation dose was estimated using CT dose index and dose length product for CT and dose coefficients recommended by the International Commission on Radiological Protection (ICRP Publication No. 106) for PET. Peripheral blood lymphocytes from both the group of patients were used for DNA damage analysis using Gamma-H2AX and olive tail moment (OTM). The differences between image quality parameters, radiation dose, and DNA damage in both the groups were compared using t-test. Results: There was no significant difference in image quality between the two protocols compared in the study. Mean contrast dose was 39.72% (54.25 ± 8.39 vs. 90 ± 0 ml; P < 0.05), effective dose was 24.34% (16.35 ± 1.73 vs. 21.61 ± 2.54 mSv; P < 0.0002), number of H2AX foci 36.47% (0.54 ± 0.07 vs. 0.85 ± 0.08; P < 0.05), and OTM 23.82% lower (24.75 ± 6.41 vs. 32.49 ± 11.38; P < 0.05) with reduced voltage and contrast-enhanced protocol compared with standard PET/CT protocol, respectively. Conclusion: Effective dose and DNA damage were less in weight-adjusted contrast enhance and lower CT voltage protocol. The image quality was acceptable for the modified protocol used here.
| OP38: Indigenously designed and fabricated container for transporting yttrium-90-labeled radiopharmaceuticals | | |
Arpit Mitra, Sreeja Menon1, Rahul Khasid2, Kamaldeep1, R. K. Gopalakrishnan1, Sharmila Banerjee2
MCF, RMC, BRIT, TMH Annexe, 2RMC, BARC, TMH Annexe, Parel, 1RSSD, BARC, Trombay, Mumbai, Maharashtra, India
Background and Objectives: Yttrium-90 (Y-90), a pure, hard β emitter (energy maximum: 2.84 MeV), with no accompanying gamma radiation, is widely used for treatment of various malignant tumors. The transportation of Y-90 from its place of production which is in Fuel Reprocessing Division, BARC, to its place of use in Radiation Medicine Centre, Parel, required covering a distance of 15 km through densely populated public road. This posed considerable challenge as lead which can stop most energetic electron is not a suitable primary shielding material and conventionally used Type A lead containers is therefore not an option for Y-90 transportation. When lead is used, the slowing down process was relatively high and the energy was re-emitted as Bremsstrahlung radiation. Shielding material with low atomic number such as aluminum/Perspex is used for attenuating β particle and lead for Bremsstrahlung. Toward this, we have designed and fabricated a primary transport container (Category–II, Type–A), where a Perspex cavity was completely encased and sealed within a modified lead container for transportation of Y-90-labeled radiopharmaceuticals. Materials and Methods: Round cylindrical Perspex block (50 mm diameter × 14 mm height, density: 1.18 g/c. c) was machined into hollow Perspex container (26 mm internal diameter [ID] × 70 mm height × 12 mm thick) with Perspex lid (8 mm height × 50 mm outer diameter) in which standard 10 mL USP type-I glass vial was placed. This whole Perspex shielding was encased within a lead container (52 mm ID × 72 mm height × 20 mm thick) which was machined using standard LP-30 lead pot. Lathe machine was used for machining. Plastic scintillation detector was used for dose measurement. Results: 200 mCi of Y-90 in a glass vial placed inside Perspex container with 12 mm thickness all around was sufficient to attenuate β energy (range in Perspex: 9.3 mm). However, 200 mCi of Y-90 after placing in 12 mm thick Perspex container re-emitted 0.243E + 08 photons/s equivalent to 0.55E + 08 MeV/s energy converted to Bremsstrahlung radiation. This 0.8% of β energy when converted to bremsstrahlung radiation was attenuated using 20 mm thick lead around Perspex. The surface contact dose rate outside the indigenously fabricated primary transport container was 50–70 μSv/h (5–7 mR/h). Conclusions: A transport container (Category–II, Type–A) for shipping of 200 mCi of Y-90-labeled radiopharmaceuticals was indigenously designed and fabricated, for the first time. Regulatory clearance for logistic purpose has been obtained for this container, and it is being routinely used for transportation of Y-90 from FRD, BARC to RMC, Parel.
| OP39: To determine the radiation burden to the personals performing positron emission tomography-computed tomography-guided metabolic biopsies of abdomen/pelvic lesions | | |
Tamanna Lakhanpal, Bhagwant Rai Mittal, Rajender Kumar, Ankit Watts, Nivedita Rana, Harmandeep Singh
Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India
Background and Objectives: With the advent of newer evolving techniques such as positron emission tomography/computed tomography (PET/CT), the sensitivity and the specificity in disease detection are greatly improved. However, imaging alone is not helpful to differentiate cancerous tissue from noncancerous one lest it specifies the tumor type. Hence, biopsy remains the most definitive diagnostic procedure for most tumors. Biopsy of lesions needs to be carefully planned and performed after correlating with findings from ultrasonography (USG), contrast-enhanced CT, magnetic resonance imaging, or other radiologic findings. However, the fear of radiation exposure looms in the interventionist mind and is of great concern. The study therefore aimed to determine the radiation burden to the personals performing PET/CT-guided metabolic biopsies of abdomen/pelvic lesions. Materials and Methods: The study was conducted at the Department of Nuclear Medicine of Post Graduate Institute of Medical Education and Research, Chandigarh. The data were collected for 22 patients having abdomen/pelvic lesions. The equipments used were PET/CT Scanner (GE Discovery ST 16), ROBIO EX machine, pocket dosimeter, and gun monitor. The patients in whom CT-guided biopsy gave nonconclusive results, prothrombin time, and international normalized ratio of the patients were in the normal range and those who agreed to give the informed written consent before intervention were included in the study. In contrast, the patients not willing to undergo biopsy or lay still for 30–45 min or with nonavailability of radiographs/USG/CT reports were excluded from the study. The whole-body exposure rate measurements were carried out using ionization chamber-based survey meter. Furthermore, the per procedure exposure measurements to the physician as well as to the physician assisting were carried out using pocket dosimeters (PDs), PD1 and PD2, respectively. The results obtained were then correlated with the ICRP-103 to see for the fulfillment of the ALARA principle. Results: The mean exposure rates measured per procedure at surface and 1-m distance from the patient were 33.09 μSv/h and 3.2 μSv/h, respectively. The mean radiation doses received by the interventionist and assistant physician per procedure were 2.09 μSv and 1.32 μSv. The calculated whole-body occupational exposure to the interventionist and assisting physician was 1045 μSv/year (2.09 μSv × 2 × 5 × 50) or 1.045 μSv/year and 660 μSv/year (1.32 μSv × 2 × 5 × 50) or 0.66 mSv/year, respectively. Conclusion: It was concluded that the PET/CT-guided biopsies are safe from radiation protection point of view.
| PP37: Assessment of exposure resulted from the delay tank facility | | |
Pankaj Tandon, Subhash C. Kheruka1, Sanjay Gambhir1
Atomic Energy Regulatory Board, 1Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
Background and objective: The study is carried out to assess the exposure rate that could contribute exposure to public from a delay tank facility of the radioiodine ward. In this study, the effluent discharge from the delay tank and the exposure rate at several locations including the delay tank surface, pipe line connected to delay tank, pipe line connected to main sewerage opening, and the room nearby the delay tank have been evaluated. Materials and Methods: To perform this study, the sample was taken from the delay tank at different points till it was discharged to the main sewerage line and was measured in a Captus 3000 well counter in cps and the radiation level in μSv/h using TBM 15D (make: Technical Associate Model: TBM 15 D) survey meter. Results: The results showed that even the facility is having one tank but because of the dilution from other hospital waste, average monthly concentration limit at the time of discharge was about 1.6 MBq/mm3, which is well below the average monthly concentration limit (22.2 MBq/mm3) of discharge of effluents from the facility prescribed by GSR-125. It has also been observed that the exposure rate is more when the delay tank is full of I-131, which is obvious but at the other nearby places also, it is below the permissible limits. The highest exposure rate level was 14 μSv/h when the delay tank was opened and the activity in the delay tank was 8.28 GBq (223.8 mCi); this is after the 4th week before releasing into the main sewerage. The exposure rate decreased up to 5 μSv/h when the door of the delay tank was closed. The exposure rate in the room near by the tank was 0.2 μSv/h, pipe line connected to delay tank was 3.3 μSv/h, and pipe line connected to main sewerage opening was 1.3 μSv/h. It was noted that exposure level was decreasing with the increase in the distance and with proper shielding. It was found that there was not much exposure to the nearby room and other area, which is 2 m away from the delay tank (0.2 μSv/h). Conclusion: At present, as per the National Regulatory Body, the delay and decay tank is a requirement for the use of radiopharmaceuticals for therapeutic purposes. However, the regulatory body is working on alternative measures so as to meet the disposable limit prescribed by the Competent Authority.
| PP38: Personnel monitoring of the staff handling 213bismuth-radiopharmaceuticals in a nuclear medicine department | | |
Parul Thakral, Jyotsna, Sunil Kumar, Renu Gemini, Suresh Pandey, Vindhya Malasani, U. N. Pallavi, Kanchan Sharma, Sugandha Dureja, Vineet Pant, Ishita Sen
Fortis Memorial Research Institute, Gurgaon, Haryana, India
Background and Objectives: Due to excellent ability of alpha particles to transfer the high amount of energy over a short tissue range, targeted alpha therapy has been attracting rising number of nuclear medicine centers. In this study, we have estimated the radiation exposure to the occupational worker during the handling of alpha emitter, bismuth-213 (Bi-213) (t1/2 = 46 min) based on the measurements with pocket dosimeter for targeted α-therapy for neuroendocrine and prostate cancer patients. The dose rates from the patients at different distances and at different time points posttherapy were also measured. Materials and Methods: This prospective study was done in the Nuclear Medicine Department, Fortis Memorial Research Institute, Gurgaon. A total of 12 patients with neuroendocrine tumor (NET) or castration-resistant prostate cancer (CRPC) were enrolled for 213Bi-DOTATOC or 213Bi-prostate-specific membrane antigen (PSMA) therapy, accordingly. Each patient received intravenous injection of 2–3 doses of 213Bi-peptide, 260–300 MBq (7–8 mCi) in a single cycle over 2–3 days. Doses to nuclear medicine personnel were assessed for different tasks such as elution, dispensing, injecting, and collecting blood samples. Radiation dose rates were measured at a distance of 1 cm and at 1 m from the patients at 0, 1, 2, and 4 h after the administration of 213Bi. Results: The mean effective doses received by a radiopharmacist during synthesis, by physicians during injection, by technologists during imaging, and by nurses during sample collection were measured using the pocket dosimeter and were found to be in the range of 2–7 μSv/procedure. The normalized dose rate per injected activity from the patients at 1 m was in the range of 0.002–0.005 μSv/MBq.h immediately after therapy. Conclusion: The study shows that the use of 213Bi-PSMA/DOTATOC for the therapy of CRPC and NET, respectively, has been simple, safe, and straightforward. The radiation absorbed doses to the occupational workers involved in different procedures were far below the dose limits prescribed by the National Regulatory Authority (20 mSv/yr). The dose rates from the treated patients pose no detrimental effect on public and environment.
| PP39: Assessment of quality assurance of nuclear medicine department having large turnover of patients: An institutional experience | | |
Bhakti Shetye
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
Background and Objectives: Optimization and dose limit are two parameters of principle of radiation protection. It involves radiation safety of nuclear medicine personal as well as patients, quality control (QC) of equipments, and estimation of radiochemical purity of various labeled pharmaceuticals. Being one of the busiest departments which handles >6000 patients per year, we undertook this study to assess quality assurance of our department. Materials and Methods: Radiation burden is mainly distributed among three people, i.e., doctors, technologists, and nurses. TLD readings of staff members for the last 5 years were studied. Before commencing daily work QC tests of two positron emission tomography/computed tomography (PET-CT) scanners and one single photon emission CT-CT systems were performed. Radiochemical purity of various labeled reconstituted kits and in-house labeled radiopharmaceuticals was assessed by ITLC method. Results: TLD reading showed the following results: For nuclear medicine, clinician's whole-body dose was in the range of 0.4–1.2 mSv. For technologist, it was 0.24–3.5 mSv, and for nurses, it was 0.9–2.68 mSv. Daily QC of gamma camera was done using Co-60 flood phantom. We evaluated parameters such as energy peak (122.0–122.8 kev), uniformity CFOV (2.05%–3.1%), uniformity UFOV (2.2–3.5%), FWHM (9%–11%). Following parameters were evaluated for daily QC of PET-CT scanners: (1) PMT gain = iterations (10–15) and average error (0.18%–0.39%), (2) energy test = energy resolution (10%–12%), (3) timing test = timing resolution (550–5561 ps), and (4) emission test = average linearity error (1.3%–1.5%). RCP of 68Ga-DOTANOC was 97%–98%, 68Ga-PSMA 98%–99%, 99mTc-DTPA 93%–98%, 99mTc-MDP 85%–92%, 99mTc-DMSA 70%–82%, 99mTc-EC 96%–98%, 99mTc-MAA 96%–98%. Conclusion: Proper planning and implementation of the ALARA principle showed received dose for all staff member below normal limit. Daily QC tests helped us to study deviation if any from its acceptable limits which further allowed us to take necessary measures. By implementation of good manufacturing practices, we got consistent RCP results.
| PV39: Awareness of radiation safety among staff nurses and radiotherapy students: Results of a comprehensive survey | | |
Nisha Bhatia, Saumya Kumari, Meenakshi Devi
Department of Nuclear Medicine, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
Background and Objectives: The increased use of ionizing radiation-based modalities such as diagnostic X-rays, computed tomographic (CT) scans, nuclear medicine scans, or therapeutic radiation has led to a multiplication of the number of examinations and hence of the overall medical as well as occupational radiation exposure. In such scenario, full awareness about the use of radiation and its protection is essential for all medical workers and medical students at an academic hospital. The study aims to (1) determine the level of knowledge and awareness on radiation safety among nurses and students and (2) assess the effectiveness of training program provided by the hospital to increase the knowledge and awareness of the hospital nurses and students. Materials and Methods: A total of 48 respondents participated in the radiation safety awareness program. In this study, target groups were nurses who were working in nonradiation areas of Cancer Research Institute and radiotherapy students. All participants (24 nurses and 24 radiotherapy students) were made to fill up questionnaires before and following the lecture on radiation safety. Survey data were collected and analyzed before and after the training. Respondents were scored out of total of 9 marks. Results: The findings showed that the percentage of total scores obtained by nurses before and after the training were 78% and 88.4%, respectively. Similarly, the percentage of total scores obtained by students before and after the training was 90.5% and 94.2%, respectively. These findings revealed that percentage score for students was higher than nurses. Before lecture, out of total 48 participants, 17 (35%) participants were afraid of radiation and 31 (65%) participants were not. After lecture, 12 (25%) participants were afraid of radiation and 36 (75%) were not afraid of radiation. It was observed that there is significant lack of awareness among hospital nurses about radiation. Conclusion: Currently, knowledge and awareness on radiation safety among the nurses are at the moderate level. Students have good knowledge about radiation safety. The results highlight that students have studied about radiation and its protection during their course, so they are better on understanding and following the radiation protection protocols. It is recommended that such radiation safety programs should be conducted on regular basis to assess and increase the level of knowledge and awareness among medical workers and students.
| PV40: Annual inspection of lead apron and thyroid shield for quality check and its rejection criteria | | |
Sachin Tayal, Abbas Ali
Kailash Cancer Hospital and Research Centre, Vadodara, Gujarat, India
Background and Objectives: Ionizing radiation used in healthcare can lead to deterministic effect (skin burn) on high exposure and increase the probability of stochastic effect (cancer); hence, radiation protection should not be compromised. The radiation safety officer should ensure periodic educational session on radiation safety for radiation workers of the facility and public/comforters educating the principles of as low as reasonably achievable and radiation-related risks. Second, the commonly used protective equipment such as lead apron and thyroid shield (by radiation workers in performing different roles or as a comforter while assisting a patient for a positron emission tomography-computed tomography [PET-CT]) is of prime importance as these acts as first line of shielding/defense and any compromise (unchecked) in the first line of defense can lead to increase in radiation exposure. Materials and Methods: Each lead apron and thyroid shield being used in the facility was assigned a unique identification alphabet and inspected under our PET-CT Scanner, Discovery STE, GE Medical Systems, USA. A standalone CT scan of the lead aprons and thyroid shields was carried out at 50 mA and 120 kV for inspecting crack/tear if any. A rejection criterion was established for the lead apron and thyroid shield made of single layer of protective material (0.25 mm Pb equivalence thickness, with a transmission actor of 0.19) being used in our facility as per the work done by Stam and Pillay. In the establishment of rejection criteria, the factor of third squared of one-tenth of the annual limit of public, 1 mSv was used since in our facility the same lead apron is used indiscriminately both for public and staff protection as and when required. Results: All the lead apron and thyroid shield inspected were in proper condition and could be used further keeping safety intact. Conclusion: Regulation should be made for submission of annual lead apron and thyroid shield inspection report annually to Competent Authority along with supporting images and calculation if any.
| PV41: Radiation safety aspects in the use of radioactivity in small animals | | |
Aruna Kaushik, Puja Panwar Hazari, Ankur Kaul, Anupama Datta, Ambika Jaiswal, Sukhvir Singh, Pradeep Goswami, Anil K. Mishra
Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Timarpur, Delhi, India
Background and Objectives: Small animals are used to elucidate diagnostic or treatment options for a disease and then translate those findings to human applications. Most clinical research utilizes mice or rats that provide useful indications of what will happen in humans. The use of radioactivity in animals for research involves administration of radionuclides in very small quantities. Safe practices need to be followed to limit the radiation doses to radiation workers to as low as reasonably achievable and for the proper disposal of the radioactive animal waste. The type of radioisotope and the amount of radioactivity administered to the animal determine the radiation safety measures. The objective of the present work is to discuss the radiation safety issues associated with handling animals injected with radioactivity. Materials and Methods: The small animals used in preclinical studies at our center include mice, rats, and rabbits. However, in this paper, an attempt has been made to address the radiation safety issues pertaining to animal studies involving mice and rats. Information on the time course of a radiopharmaceutical in these animals is obtained by performing invasive or noninvasive (preclinical imaging) biodistribution studies. The radioisotopes commonly used for labeling at our center include 99mTc, 18F, 68Ga, and 11C. The animals are sacrificed in invasive biodistribution studies and activity in the tissues is quantified. Noninvasive biodistribution studies involve imaging the animals under a scanner in static and dynamic modes and quantifying the uptake of radioactivity in various organs or tissues. The details regarding the type of radioisotope, amount of radioactivity injected per mouse, and the number of mice used per sample are summarized in [Table 1] for invasive procedures and noninvasive imaging. Results and Conclusion: The specific gamma ray constant for positron emitters is approximately ten times of 99mTc. Appropriate shielding should be provided for the type of radioisotope involved. Further, these studies should to be performed in the research laboratories (Type I, Type II, or Type III) meeting all the safety requirements of shielding, ventilation, storage, and appropriate waste disposal methods. | Table 1: Biodistribution studies involving invasive procedures and noninvasive imaging
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| Radiopharmaceutical Development Track | | |
| OP42: Ready-to-use 177Lu-trastuzumab formulation and its molecular studies in HER2-positive breast cancer cells | | |
Rohit Sharma, Mythili Kameswaran, Usha Pandey, Naresh Gamre, Ashutosh Dash
Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Radiolabeled monoclonal antibodies are efficient tools for cancer therapy. Combination of 177Lu (Eβ−max = 497 keV, Eγ = 0.208 MeV and t1/2 = 6.7 days) with trastuzumab could make it a promising radioimmunotherapeutic agent for HER2-positive breast cancers. In this study, we have reported the preparation of 177Lu-CHXA”- DTPA-trastuzumab formulations and its reproducibility in terms of stability and specificity over a period of time. To elucidate the mechanism of action of RIT at the cellular and molecular level with 177Lu-trastuzumab, HER2-positive breast cancer cells MDA-MB-453 were treated with 177Lu-CHXA”-DTPA-trastuzumab. Materials and Methods: Multiple batches of177Lu-CHX-A”-DTPA-trastuzumab were prepared as ready-to-use formulations. The radiochemical purity (RCP), stability, and specificity of the formulations were determined at different intervals of time. Pharmacokinetic studies were performed in normal Swiss mice to determine the pattern of uptake and clearance of the formulation. Cell toxicity studies and apoptosis and cell cycle analysis were carried out in HER2-positive cells to determine the mode of cell death. Results: RCP of the all the formulations was ascertained to be >95% up to 120 h postpreparation as determined by SE-HPLC. In vitro cell-binding studies showed uptake which was inhibited on coincubation with cold antibody indicating the specificity of the radioimmunoconjugate. Cellular studies revealed a dosedependent cellular toxicity. Mode of cell death was by apoptosis. The complex showed retardation in the S phase of cell cycle with twofold increase in G2/M arrest, which could possibly be the reason for enhanced apoptosis at higher doses. Biodistribution studies in normal Swiss mice revealed clearance primarily through the hepatobiliary route. Conclusion: The results from the in vitro and in vivo studies indicate the potential of 177Lu-CHXA”-DTPA-trastuzumab as a promising radioimmunotherapeutic agent for HER2-positive breast cancer patients.
| OP43: Standardization of radiolabeling and quality control methods for commercially available BRIT [99mTc]Tc-TRODAT-1 kits: NIMHANS experience | | |
Raman Kumar Joshi, Pardeep Kumar, R. Gopinath, S. Dinesh Kumar, Chandana Nagaraj, Jitender Saini, Arun K. Gupta
Neuroimaging and Interventional Radiology, NIMHANS, Bengaluru, Karnataka, India
Background and Objectives: Parkinson's disease is a degenerative disorder of the central nervous system which involves loss of dopamine neurons as a characteristic feature. TRODAT-1 is propane derivative having a high binding affinity for the dopamine transporter (DAT) receptors. [99mTc]Tc-TRODAT is choice of scan. We have difficulty in obtaining good-quality standard images. The study aims to troubleshoot radiolabeling and quality control procedure to obtain standard images with [99mTc]Tc-TRODAT kit. Materials and Methods: The single vial TRODAT-1 kits and [99mTc] was procured from Regional Centre of BRIT, KIDWAI Campus, Bengaluru. The radiolabeling was performed as per the manufacturer instruction with few modifications. Briefly, 60 ± 5 mCi of [99mTcO4-] (in a volume of 700 ± 100 μL of saline) was added to the kit, and the contents were mixed and kept for incubation at 95°C for 45 min. The vial mixture was shaken at every 5 min during the incubation. The radiochemical purity was checked by using instant thin layer chromatography (ITLC) on silica gel strip (silica gel 60) using saline as a solvent. The stability of the labeled kit was evaluated up to 4 h after reconstitution. The ITLC strip (10 cm × 1 cm) scanned for 7 min on TLC scanner (EZ scan, California, USA) with a speed of 2 cm/min. After passing quality control, the labeled 99mTc TRODAT 20 ± 5 mCi was injected into the patients. Following the injection, whole-body sweep images were acquired 30 min postinjection to look for biodistribution and labeling efficiency. This was then followed by single photon emission computed tomography (CT)-CT imaging of the brain 4 h postinjection. Results: The pH of the final preparation was 6.6 ± 0.5. The ITLC method showed retention time of 5.8 ± 0.6 min for [99mTc] and 2.1 ± 0.6 [99mTc]Tc TRODAT-1. The labeling efficiency was found to be 93.5% ± 2.5% and no degradation was found in the radiolabeling up to 4 h at room temperature. Diffuse tracer uptake was noted in the brain, nasal mucosa, bilateral lungs, liver, and intestines in whole-body sweep images at 30 min. No uptake seen in the thyroid, salivary, and stomach confirmed the absence of any free pertechnetate. Conclusion: The modified standard operating protocol helps us to standardize the procedure as per our laboratory conditions. The standardization in labeling has made improvement in the distribution of the [99mTc]Tc-TRODAT-1.
| OP44: Toxicity evaluation of chitosan-coated iron oxide nanoparticles as a function of concentration | | |
Nimisha Jaia, Sanjay Bharati, Shivanand Bhushan
Department of Nuclear Medicine, SOAHS, MAHE, Manipal, Karnataka, India
Background and Objectives: Chitosan is a biological compatible molecule that can be modified for a variety of nuclear medicine imaging and therapeutic applications. The aim of the present study was to find out the toxicity of chitosan-coated iron oxide nanoparticles (CMNPs) at 5, 15, and 45 mg/kg body weight in mice after 24 h and 30 days. Materials and Methods: The male Balb/c mice were divided into four groups. Group II, III, and IV received a single intravenous CMNPs injection at doses 5, 15, and 45 mg/kg body weight. Group I served as control and was administered normal saline. The toxic effects in mice were assessed in terms of the activities/levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine amainotransferase (ALT), urea, and creatinine. Histopathological examination of the liver and kidney tissues were carried out to determine the presence of any histoarchitectural changes. The status of enzymatic and nonenzymatic defense system in the liver was also assessed at both the time points. Results: The results showed no pathological changes and nonsignificant alterations in LDH, AST, ALT, urea, and creatinine after 24 h or 30 days of CMNPs administration. Nonsignificant changes were observed in the status of antioxidant and nonantioxidant defense system. Conclusion: The results could be a promising outcome, leading to the extension of our knowledge on CMNPs and their possible medical applications in diagnostic and therapeutic field.
| OP45: Design, synthesis, and evaluation of a new 68Gallium-labeled chelator-conjugated bisphosphonate for imaging skeletal metastases by positron emission tomography | | |
Sudipta Chakraborty, Dibakar Goswami1, Rubel Chakravarty, H. D. Sarma2, Ashutosh Dash
Divisions of Radiopharmaceuticals, 1Bio-organic and 2Radiation Biology and Health Sciences, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Since the introduction of 68Ge/gallium-66 (68Ga) generator in clinical practice, a few 68Ga radiopharmacals have been extensively used for noninvasive monitoring of caner by positron emission tomography (PET). However, a suitable 68Ga-radiopharmaceutical for early diagnosis of skeletal metastases is of great demand in nuclear medicine. We report herein the design, synthesis, and evaluation of 68Ga-complex of a new chelator conjugated bisphosphonate ligand namely, NOTA-Bn-SCN-BP, for its potential use in imaging skeletal metastases by PET. Materials and Methods: NOTA (1, 4, 7-triazacyclononane)-conjugated germinal bisphosphonate was synthesized in a three-step process by coupling aminoethyl bisphosphonic acid with p-NCS-Bn-NOTA in the final step. The ligand was purified by HPLC and characterized by 1H NMR, 31P NMR, and mass spectrometry. 68Ga complex of the ligand was synthesized at room temperature by mixing 0.5 mL of 68Ga eluate in 0.05 M HCl and 25 μg of ligand dissolved in 0.5 mL of 0.25 M sodium acetate buffer (pH ~4). The complex was characterized by ITLC-SG and radio-HPLC. In vitro stability of the formulation was evaluated in isotonic saline and human serum at 37 degree C. Biological efficacy of the formulation was evaluated by carrying out ex vivo biodistribution studies in normal Wistar rats. Results: 68Ga-NOTA-Bn-SCN-BP was synthesized with a radiochemical purity of 98.3% ± 0.4% at room temperature. The complex exhibited excellent in vitro stability in isotonic saline and human serum. Biodistribution study carried out in normal Wistar rats showed that the synthesized formulation has fast accumulation in skeleton (2.81% ± 0.33% injected dose per gram in femur at 30 min postinjection) with almost no retention in any other organ/tissue. The radioactivity nonaccumulated in the skeleton execrated rapidly through renal route. Conclusion: The newly synthesized molecule NOTA-Bn-SCN-BP would be a promising targeting ligand for the development of a potent 68Ga-radiopharmaceutical for imaging skeletal metastases by PET.
| OP46: Design, synthesis, and comparative evaluations of Gd-DO3AM-Propyl-1-2-methoxyphenylpiprazine and Gd-DO3A-Propyl-1-2-methoxyphenylpiprazine conjugate as chemical exchange saturation transfer-magnetic resonance imaging contrast reagents | | |
Anju Wadhwa1,2, Shubhra Chaturvedi2, Deepa Bhadouria2, Firasat Hussain1, A. K. Mishra2
1Department of Chemistry, University of Delhi, North Campus, University Enclave, 2Division of Cyclotron and Radiopharmaceutical Sciences, INMAS, DRDO, Timarpur, Delhi, India
Background and Objectives: In vivo mapping of receptors, especially neuroreceptors, using magnetic resonance imaging (MRI) is beset due to the low sensitivity of the technique. Chemical exchange saturation transfer (CEST) offers better sensitivity than MRI and can be used for low concentration metabolite tracing. The electron distribution at the paramagnetic metal center and consequently exchange rate with the surrounding water influences the CEST-MRI signal strength agent. DOTA-Gd derivatives have been widely reported for CEST-MRI. Thus, in the present work, we developed two analogs of cyclen-conjugated triacetate and triamide Gd-based CEST-MRI agent (Gd-DO3A-Propyl-1-2-methoxyphenylpiprazine [MPP] and Gd-DO3AM-Propyl-MPP) and comparatively analyzed the relaxation rate and signal intensity for 5-HT1A receptor imaging. Materials and Methods: As first step, cyclen was substituted with two different reagents using three moles of each di-tert butyl dicarbonate and tert-butyl bromoacetate resulting triboc cyclen DO3AM and DO3A, respectively. Then, each trisubstituted cyclen was conjugated with MPP through 1-bromo-3-chloropropane linker. The resulting analog was deprotected appropriately using TFA/DCM for DO3A and concentrated HCl/MeOH for DO3AM. The resulting complexes were characterized using various analytical techniques. Lanthanide complex of each analog was synthesized from equimolar quantities of ligand and gadolinium chloride at 60°C in water, and the complexes were characterized after purification with HPLC. Stability constant of metal complexes was evaluated using in silico density functional theory (DFT) and by potentiometric titration. Using the membrane extracts of hippocampus, the complexes were compared for relaxation rates. Results: The macrocycles DO3AM-MPP and DO3A-MPP were synthesized in 40% and 60% yield, respectively. The purity of the final compounds was further confirmed by HRMS and HPLC. Complexation of each analog with GdCl3 has been performed and HPLC profiles have been established using methanol-water as the mobile phase. DFT calculations are underway. Potentiometric calculations show high stability for the complexes. Future work will concentrate on the comparison of relaxation rates using 5HT1A-rich membrane extracts of the hippocampus. Conclusion: Gd-DO3AM and Gd-DO3A complexes were synthesized and used as CEST-MRI contrast reagent to measure relaxation rate.
| OP47: A multimodal neuroimaging agent for human 5-HT1A/5-HT7 receptors | | |
Preeti Jha1,2, Shubhra Chaturvedi2, Ankur Kaul2, Puja Panwar Hazari2, Nidhi Jain1, A. K. Mishra2
1Institute of Nuclear Medicine and Allied Sciences, 2Indian Institute of Technology, Delhi, India
Background and Objectives: The 5-HT1A and 5-HT7 receptors are highly coexpressed as monomers and oligomers in specific brain regions and responsible for modulating serotonergic signaling. Under depressed conditions, the signaling of 5-HT1A receptors gets modulated by 5-HT7 receptors in the central nervous system. This complex signaling mechanism includes structural reorganizations such as dimerization, altering the synaptic gradient of these receptors. Hence, imaging of 5-HT1A/5-HT7 receptors either inmonomeric or dimeric states under physiological and pathological environment can be employed to track the quantitative/functional facet of neurological disorders. At present, we report design and development of a multimodal 11C-PET/99mTc-single photon emission computed tomography-based radioligands for targeted in vivo imaging of human 5-HT1A/5-HT7neurotransmitters. Materials and Methods: Two hybrid ligands – [CH3]-BTZ-MPP and DTC-BTZ-MPP – were constructed using benzothiazolone (BTZ) and methoxyphenylpiperazine (MPP) pharmacophores. Screening was performed using well-established 3D-models of h5-HT1A and h5-HT7 receptors. Synthesis involved multi-step protocol, where all intermediates and final compounds were characterized using spectroscopic and analytical techniques. MTT and hemolysis assays ensured biocompatibility. Radiolabeling with 11C and 99mTc-radioisotopes was carried using 11CH3I and Na[99mTcO4] and optimization of radiolabeling conditions was thoroughly studied. HPLC profiling and HRMS were performed for the characterization of 11C-based radiotracer, while ITLC was used for investigating 99mTc-labeling efficiency. Depressed/stressed mice models were developed using long-term corticosterone treatment. Results: In silico analysis revealed essential residues (Asp116, Lys191, Ser199, Ile189 and Asp162, Val163, Phe343, Phe344) in the binding pocket of 5-HT1A and 5-HT7 receptors. The partition coefficient of [11CH3]-BTZ-MPP and [99mTc]-DTC-BTZ-MPP came out to be 1.26 and 1.8, respectively, supporting blood–brain barrier penetration. All compounds were synthesized in >90% global yields, wherein purity was ensured NMR, HPLC, and HRMS. Lead compounds were found nontoxic. Appreciable-specific brain uptake was noted in noninvasive imaging. Biodistribution showed maximum brain uptake of 13.37% ± 1.2% ID/g and 11.95% ± 0.4% ID/g in treated and normal mice at 15 min p.i. for [11CH3]-BTZ-MPP, while 2.06% ± 0.01% ID/g and 1.38% ± 0.01% ID/gfor [99mTc]-DTC-BTZ-MPP, respectively, under similar circumstances. The affinity toward 5-HT1A/5-HT7 receptors was noticed via a significant uptake in hippocampus and cortex. Hepatobiliary route of excretion was indicated as major radioactivity accumulation of radiotracers was spotted in lungs and liver. Conclusion: A new multimodal positron emission tomography/single photon emission computed tomography-based brain imaging agent was screened and synthesized to selectively map the h5-HT1A/5-HT7 receptors. Substantial brain permeation and favored radioactivity accumulation in specific receptor-rich brain regions were observed in the preclinical evaluations, suggesting promising venture for delineating neurological disorders.
| OP48: Nucleoside-capped surface modified silver nanoparticles as dual imaging agent | | |
Deepa Bhadouria1,2, Anil K. Mishra2, Shubhra Chaturvedi2, Anju Wadhwa2, Vishakha Chaudhary2, Sangeeta Lal3, Ankur Kaul2, Sunil Pal2, Aruna Chhikara4
1University of Delhi, 2INMAS, DRDO, 3School of Physical Sciences, Jawaharlal Nehru University, 4Dyal Singh College, University of Delhi, Delhi, India
Background and Objectives: The bioapplications of silver nanoparticles (Ag-NPs) include antimicrobial, anti-inflammatory, and anti-angiogenic agents. However, the utility of Ag-NPs is restricted due to the associated toxicity. These limitations can be addressed by appropriate surface modification of the nanoparticles which include appending with small biomolecules. To enhance the biocompatibility and cellular internalization, Ag-NPs have been appended with ketalized nucleoside. Since nucleosides uptake is enhanced in tumor cells, nucleoside appended Ag-NPs are hypothesized to have better efficacy, greater cellular accumulation, and better biocompatibility. In addition, the nucleosides at the surface of the Ag-NPs will provide site for 99mTc labeling. The resulting nanoparticles can thus be tracked using 99mTc-single photon emission computed tomography (SPECT) imaging or can also be visualized through optical imaging owing to the high extinction coefficient of Ag. The surface modification of the Ag-NPs has been carried out using diethylene triamine pentaacetic acid dianhydride (DTPAA). Materials and Methods: The synthesis involves ketalization at 2',3' of uridine (DAU), followed by azidation at 5' position (DAU-N3). DAU-N3 was further reduced to amine and then conjugated with DTPAA. The Ag-NPs were synthesized by electroexplosion of wire technique. DAU-DTPAA was then appended with Ag-NPs to yield surface modified Ag-NPs. The compounds were thoroughly characterized using spectroscopic methods. Results: The final compound DAU-DTPA was synthesized with 80% yield. Surface modification of the Ag-NPs has been carried using DAU-DTPAA and has been confirmed by TEM, FT-IR, and UV-vis spectroscopy. The TEM images show highly dispersed and uniform particles. Radiolabeling with 99mTc has been carried out with more than 98% efficiency. Imaging and biodistribution studies are underway. Conclusion: Biocompatible nucleoside-appended Ag-NPs have been synthesized to serve as dual imaging agent.
| OP49: Design, synthesis, and evaluations of blood–brain barrier permeable ferrocene-conjugated complex 99mTc-Fc MPP (DO3A) as single photon emission computed tomography imaging neurotracer | | |
Vishakha Chaudhary, Anil Kumar Mishra, Shubhra Chaturvedi, Amita Malik1, Ankur Kaul, Deepa Bhadouria, Anju, Sunil Pal
INMAS, DRDO, 1Delhi Universities, Delhi, India
Background and Objectives: Delivery of drugs across natural barriers, especially blood–brain barrier (BBB), has been the focus. Based on the observation that appending organometallic group to drugs facilitates their cellular and BBB permeation, we hypothesize that neuro-receptor-targeted ligands can be made to permeate the BBB using the same approach. The metallocene not only provides a hydrophobic handle for membrane translocation but also facilitates the localization and distribution of the conjugate in the cytoplasm. To test this hypothesis, methoxyphenylpiperazine-conjugated ferrocene derivative has been synthesized and evaluated for brain permeability. We have synthesized radiotracer (Fc-MPP-(DO3A)) using ferrocene and 5HT1A antagonist methoxyphenylpiperazine, further conjugated with DO3A, and radiolabeled it with 99mTc for receptor imaging. Materials and Methods: At first step, 2-bromoethylamine hydrobromide was protected with di-tert-butyldicarbonate. In the next step, 2-(Boc – amino)ethyl bromide was conjugated with N-(2-methoxyphenyl)piperazine (MPP). The resulting analog was deprotected using TFA/DCM. Then, the deprotected analog which we get from the last step was conjugated with ferrocenecarboxaldehyde and then it reduced using Pd/C, and further conjugated with DO3A for receptor imaging. The resulting complexes were characterized using various analytical techniques. Results: The yield of the final compound was between 60% and 70%. The compound was purify by column chromatography and characterized by NMR and HRMS. The cytotoxicity of the 99mTc-MPP(DO3A) complex to HEK cell was investigated using MTT assay. Conclusion: 99mTc-Fc MPP(DO3A) was synthesized and used as single photon emission computed tomography imaging neurotracer. In conclusion, this work supports the bioorganometallic conjugation for enhance brain delivery.
| OP50: In-house radiosynthesis of [11C] choline radiotracer for clinical use: our initial experience | | |
Sunil Kumar
DSCI, Delhi, India
Background and Objectives: [11C]-choline is a proven positron emission tomography (PET) tracer for imaging of neoplastic and metastatic lesions of prostate cancer (PC). The production of [11C]-choline is a challenging process for manufacturers. The study aims to synthesize batch production of [11C]-choline in automated synthesizer module for in-house clinical use. Materials and Methods: [11C] CO2 was produced from the nuclear reaction on the gas mixture of N2 + O2 gas in gas chamber target in cyclotron (GE PETtrace 860) via (14N[p, a]11C) at 40 μA for 20 min and produced 900 ± 60 mCi of [11C] CO2. [11C] CO2 was transferred to methane oven in GE Tracerlab FX2C module at flow rate of 120 mL/min in 90 s where it was reduced (Ni, H2 [g], 350°C) to [11C]CH4. [11C]CH4 was then reacted with iodine (740°C furnace) to provide [11C]CH3I (methyl iodide), which was subsequently passed through CM Sep-Pak cartridge containing 60 μl of dimethylaminoethanol precursor at a flow rate of 20 mL/min for 3 min. The Sep-Pak was washed with 10 ml of ethanol (from reservoir above V6) and 10 ml of water (from reservoir above V5). The product was eluted with 5 ml of normal saline (from reservoir above V4). Synthesis took around 20 min. The final dose was transferred into a sterile vial through 0.22 mm sterile filter and a small volume was sent for quality control testing. Results: The final average yield of the [11C] choline was 35% ± 5%. Total number of [11C] choline batches produced = 17 in the duration of 14 months. Total [11C] choline produced was 4550 mCi which is sufficient for 66 patients due to short half-life (T1/2 = 20 min). Only one production failed due to weak cable connection from inside of module. Conclusion: [11C] Choline has been successfully synthesized in short time with high radiochemical yield and purity. Till date, around 66 PC patients have undergone [11C] choline PET scan at our center.
| OP51: Radiolabeling optimization of 99mTc-ranatensin-based radiopeptides for targeting bombesin receptors | | |
Ajay Kumar, Baljinder Singh, Raunak Varshney1, Anil K. Mishra1, Shalini Chopra, Sarika Sharma, Amritjyot Kaur
Department of Nuclear Medicine, PGIMER, Chandigarh, 1Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India
Background and Objectives: Both gastrin-releasing peptide and neuromedin B receptors (GRPr and NMBr) are overexpressed in prostate cancer. The ranatensin peptide has high affinity for both these receptors. Thus, GRPr and NMBr antagonists can be used as cancer-targeting vectors to shuttle diagnostic and therapeutic agents into tumor cells. The objective is to optimize the radiolabeling of ranatensin peptide analogs with 99mTc for targeting GRPr/NMBr. Materials and Methods: The ranatensin peptide analogs DOTA-6Ahx-Aib-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 and DOTA-Aib-Gln-Val-Gly-His-Leu-Met-NH2 were purchased from link Biotech. For optimization of radiolabeling of DOTA-ranatensin-peptide with 99mTc, various reaction parameters were studied, which include peptide amount (50, 100, 150, 200, and 250 μg), amount of stannous chloride (5, 10, 15, 20, and 25 μg), choice of buffer, stabilizing agent, incubation time, and filtration. The radiochemical purity of the peptide conjugate was estimated using instant thin layer chromatography (ITLC-SG strips as stationary phase and 100% acetone as mobile phase). The radio colloids were also detected in labeled product using a cocktail of pyridine/acetic acid/water (3:5:1.5) as mobile phase. Results and Conclusion: The radiochemical purity of 99mTc-labeled peptide conjugate was >90.0% with 150.0 μg of the peptide dissolved in 5.0 μg of stannous chloride, 10.0 μl of ascorbic acid, and 99mTcO4 (70–80 MBq) with 30 min of incubation time at room temperature. The pH was set to 7.0 using 10.0 μl of 0.5M NaHCO3. It was observed that postlabeling filtration reduced the labeling efficiency to 70.0% as compared to the prelabeling filtration. Thus, both the ranatensin peptide analogs were optimally labeled with 99mTc-pertechnetate indigenously and will now be subjected to further quality control procedures before preclinical evaluation in normal and tumor animal model.
| OP52: Evaluation of acetamidobenzoxazolone derivatized biomarkers for assessing translocator protein in brain and peripheral organ | | |
Pooja Srivastava, Anjani K. Tiwari1, Ankur Kaul2, Lalita Mehra
Department of Combat Sciences, Institute of Nuclear Medicine and Allied Sciences, 2Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, 1Department of Chemistry, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
Background and Objectives: Translocator protein (18 kDa, TSPO) has a great role in activation of glial cells in the injured brain as well as in inflammatory condition. It has found that TSPO expression is markedly upregulated in inflammation conditions and easily correlated to the extent of microglial activation, making the quantification of TSPO density a standard indicator for brain diseases. Recently, it has found interesting and correlative in inflammatory conditions of peripheral organs. The objective of the study is to evaluate the diagnostic approach of newly synthesized molecule acetamidabenzoxazolone-amino acid ester (ABO-AA), where AA is tryptophan methyl ester (T), in rodents as well as specific animal models for inflammatory condition of brain/lungs. Materials and Methods: ABO-T has been labeled with 99mTc and biologically evaluated for imaging of TSPO expression. The ADME property has been assessed computationally and by tracer methods. To determine specific binding of this compound, blocking study was performed with TSPO specific compound PK11195. Characterization and validation of all synthesized compounds were done with different spectroscopic techniques (NMR and MS). G Score was obtained from CADD studies. Results: Target molecule ABO-T was synthesized in good yield by easily repetitive chemical methods. Docking analysis of synthesized ligands and co-crystallized ligand was performed on 4RYO which also validated our hypothesis. Specific binding with TSPO on neuroinflammation as well as inflammation in peripheral organs were found appropriate as per the existing compounds. Single photon emission computed tomography (SPECT) biodistribution studies in mice revealed the maximum brain uptake at 2–5 min postadministration in traumatic brain injury model. The localization of radiolabeled drug is mainly in lungs, liver, spleen, and kidney, which are TSPO-rich organs. The dynamic scintigraphic scan carried out on rat correlated with findings of organ distribution study. Conclusion: On the basis of animal biodistribution data and SPECT images, ABO-T has shown promising aspect to image TSPO in both central nervous system and peripheral organs. Further primate & rsquo's study is required to evaluate the usefulness of this compound before clinical use.
| OP53: Modified third-generation translocator protein-selective positron emission tomography radiotracer to access microglial activation in ischemic rat brain | | |
Anjani K. Tiwari, Pooja Srivastava1, Praveer Kumar2, Anil K. Mishra1
Department of Applied Chemistry, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 1Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, 2Department of Biotechnology Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University, Delhi, India
Background and Objectives: Translocator protein (TSPO) is an efficient biomarker to trace neuroinflammation. The quantification of TSPO density in a tissue region can be used as a tool for monitoring for recovery after treatment or for the progression of disease. In this work, we have designed third-generation TSPO ligands which overcome most of the problems of first and second generation. Hence, herein, we report the synthesis and biological evaluation of 11C-MABO for positron emission tomography (PET) imaging in ischemic rat brain. Materials and Methods: CADD were used for screening of best compound; subsequently, synthesis was performed. Synthesis was employed by convergent methodology in high yielding steps. In vitro assay was performed to determine the binding affinity in terms of Ki for the synthesized ligands; the in vitro assay was performed to determine the binding affinity in terms of Ki. Ischemic rat brain was used to check the specificity and affinity of the designed radiolabeled ligand for TSPO. Results: G Score for MABO was found much appropriate in comparison to the reference ligand promoted it for wet laboratory synthesis. Synthesis of MABO was successfully carried out and characterized by spectroscopic techniques. In vitro binding assay showed high binding affinity Ki = 5.6 + 0.5 for PBR (TSPO) over central benzodiazepine receptor Ki >200. Displacement experiments with unlabeled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand toward TSPO receptor. Conclusion: Radiopharmaceutical evaluation in ischemic rats have proved [11C]MABO as a potential PET imaging agent for TSPO targeting.
| PP40: Production and supply of ready to use 68Ga radiopharmaceuticals: BRIT experience | | |
Anupam Mathur, Soumen Das1, Dheeraj Kumar1, Kiran Mehra1, P. C. Vrinda1, S. Mirapurkar1, Chanda Arjun1, K. Barakha1, S. Ravi1, S. S. Sachdev1
Radiopharmaceuticals Programme, Board of Radiation and Isotope Technology, Navi Mumbai, Maharashtra, 1Radiopharmaceuticals Programme, Board of Radiation and Isotope Technology, India
Background and Objectives: Availability of 68Ga, a positron emitter, through a long lived 68Ge-68Ga generator system has facilitated the growth of positron emission tomography (PET) technology and will be the mainstay of diagnostic nuclear medicine in the near future. Currently, 68Ga imaging is restricted to nuclear medicine centers equipped with in-house 68Ge-68Ga generator facility due to its short half-life of 68 min. Although the radionuclide is short lived, there is a commercial interest to explore the feasibility of production and supply of its labeled radiopharmaceuticals via a centralized radiopharmacy, similar to 18F-labeled radiopharmaceuticals, to nearby PET centers located in close vicinity to centralized production unit. In this preview, 68Ga-DOTA-TATE and 68Ga-PSMA labeling protocols were standardized and logistics evaluated for its regular production and supply using a 50 mCi 68Ge-68Ga generator. Materials and Methods: 68Ge-68Ga generator (50 mCi) along with semi-automated shielded synthesis module was obtained from ITG, Germany. Elution profile of 68Ga activity eluted out from the generator using 0.05 M HCl was monitored over a period of 15 days. Total six batches of 68Ga-labeled RPhs, viz., 68Ga-DOTA-TATE and 68Ga-PSMA, were prepared as per the approved radiochemical purity (RPC) monograph. The production was optimized with respect to time for different stages of production starting from elution of 68Ga activity to labeling with peptide ligands, purification, sterilization, quality control analyses, and final packing of 68Ga-labeled radiopharmaceuticals. The product 68Ga-DOTA-TATE/PSMA was observed for stability up to 4 h at room temperature to ascertain the transportation conditions. Results: The theoretical elution efficiency of the generator observed was around 85%. The total production time for both labeled radiopharmaceuticals post-68Ga elution was around 0.5 h. The activity observed in the labeled radiopharmaceutical poststerilization was around 25 mCi. This was lower to the expected total 68Ga activity (30 mCi). Around 15% of the labeled radiopharmaceutical was lost on sterilization filter and other transfer losses. The RCP observed up to 4 h was >90% as per the RPC monograph. The product can be shipped to the customers post-BET and RCP testing. The total production period including radiolabeling and quality control analyses (RCP/BET) for all the batches were complete within 1 h post-68Ga elution and the total activity available at the time of shipment is around 20 mCi. Conclusion: Only one or two patient doses (3/5 mCi) of 68Ga-labeled radiopharmaceuticals (DOTA-TATE/PSMA) can be produced from a 50 mCi generator for consumption within 3 h postproduction up to a period of 6 months.
| PP41: Targeting efficiency of 99m-technetium-labeled polymeric nanoparticles | | |
Swapna Nair, Alka Mukne, R. Krishnamohan1, Aruna Korde1
Bombay College of Pharmacy, 1Department of Radiopharmaceuticals, Bhabha Atomic Research Center, Mumbai, Maharashtra, India
Background and Objectives: Nanosized particles can be easily transported to different sites in the body and may be effective in enhancing the efficacy of drugs. The present study involves preparation of polymeric nanoparticles for targeted delivery to organs rich in macrophages. Materials and Methods: Modified polymeric nanoparticles were prepared for targeted delivery to the macrophage-rich organs. The formed nanoparticles were labeled with 99m-technetium using sodium borohydride as the reducing agent. Biodistribution of the formulation in different organs (including liver, lungs, spleen, and kidneys) of Wistar rats was evaluated at various time intervals (0.5, 1, 3, 6, 12, and 24 h). Results: A consistent radiolabeling yield of 95% was observed using the developed method. Biodistribution studies of the formulation revealed maximum localization in the lungs and liver after 6 h. Time-dependent increase in radioactivity was observed in these organs, whereas the least amount of radioactivity was observed in the heart and stomach. Conclusion: The results of the study demonstrate that the nanoformulation can be developed for targeted drug delivery to or imaging of macrophage-rich organs.
| PP42: Development and standardization of a new method for the detection of radiochemical and chemical purity of the positron emission tomography radiopharmaceuticals | | |
Pardeep Kumar, Raman Kumar Joshi, Chandana, Arun K. Gupta
Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
Background and Objectives: Quality control (QC) plays an important role in the production and administration of the positron emission tomography (PET) radiopharmaceuticals into the patients. The study aims to standardize and develop a radio-TLC, radio-HPLC, and GC protocol for [18F]-FDG and [13N]-NH3. Materials and Methods: [18F] and [13N] are produced at our on-site cyclotron (GE Pettrace 860). [18F]-FDG was synthesized by the standard protocol in the GE automated MX module. [13N]-NH3 was produced by the reaction of sodium hydroxide with 13NO3-/13NO2- in the presence of DeVarda alloy. Radio-TLC was performed on TLC scanner with a speed of 2 cm/min using 95% acetonitrile as a solvent for [18F]-FDG and 75% methanol for [13N]-NH3. Radio-HPLC was performed on Dionex, Thermo-Fisher HPLC equipped with UV/Vis, and radiodetector using 50 mM NaOH as a solvent at a flow rate of 0.3 mL/min and Dionex Carbo-Pak Pa-1 (2 × 50 mm) as a stationary phase for [18F]-FDG. The cold fluorodeoxyglucose was used as a control and measured at UV-220 nm. For HPLC of [13N]-NH3, 95% acetonitrile used as a solvent and acclaim polar advantage (C16, 3 mm, 2.1 mm × 100 mm) as a stationary phase. GC was done for [18F]-FDG on Scion GC-436 equipped with FID. The column was operated initially at 40°C for first 3 min and then rise 50°C/min up to 8 min, and the final temperature was set at 240°C and the column was BR-200 ms, 0.32 mm ID. The makeup gas consists of helium (28 mL/min), zero air (300 mL/min), and hydrogen gas (30 mL/min) flow at the rate of 2 mL/min. Results: TLC method for [18F]-FDG is very well established (1.9 ± 0.4 min for [18F] and 4.6 ± 0.3 min for [18F]-FDG). Retention time was 5.8 ± 0.6 for [13N]-NH3 min as compared to 2.4 ± 0.4 min for 13NO3-/13NO2-. Radio-HPLC retention time for cold fluorodeoxyglucose was 3.6 ± 0.5 min (UV/Vis), [18F]-FDG was 4.1 ± 0.6 min, and free [18F] was 2.3 ± 0.3 min (radio-detector). Radio-HPLC peaks for 13NO3-/13NO2- was at 1.2 ± 0.4 min and 2.4 ± 0.3 for [13N]-NH3. GC analysis showed ethanol was 105 ± 15 ppm and acetonitrile was 10 ± 5 ppm in [18F]-FDG, well below the prescribed limit. Conclusion: HPLC is quick and reliable but expensive method, whereas TLC is convenient, cheap and as accurate as HPLC. Therefore, TLC can be used for routine QC. The optimized methodology shows good reproducibility; thus, it could be successfully applied in the QC of the radiopharmaceuticals.
| PP43: Evaluation of 99mTc-methoxy isobutyl isonitrile formulation prepared by microwave assisted radiolabeling procedure | | |
Krishna Mohan Repaka, Krishna Mohan Repaka, Anupam Mathur, V. V. Murhekar, D. Padmanabhan
Board of Radiation and Isotope Technology, India
Background and Objectives: 99mTc-methoxy isobutyl isonitrile (MIBI) is a myocardial perfusion agent used in diagnostic nuclear medicine. The labeling procedure involves heating of 99mTcO- with MIBI kit under boiling water conditions for 10 min. Each kit contains 1 mg of [Cu(MIBI)4]BF4 ligand. Microwave heating is a known methodology to improve the reaction kinetics with reduced molar content of the reactants. The present study aims to optimize the labeling protocol of 99mTc-MIBI, using rapid microwave heating method with reduced [Cu(MIBI)4]BF4 concentration so as to obtain final labeled radiopharmaceutical suitable for clinical use. Materials and Methods: Varying amounts of [Cu(MIBI)4BF4] ligand (0.1–1 mg) were chosen for the study keeping the other kit components, viz., SnCl2.2H2O, L-cystiene, sodium citrate tribasic dehydrate, and mannitol same. 99mTcO4- used for preparation was in the range of 5–30 mCi. 99mTc-MIBI labeling was carried out using microwave heating with commercially available microwave (10 s and 400 W). Radiochemical purity of 99mTc-MIBI was determined using RPC approved method. The physiological distribution studies were carried out in Wistar rats (n = 3) as per the RPC guidelines. The formulations were also studied for their stability up to 24 h postlabeling. Results: The radiochemical purity of 99mTc-MIBI labeled using microwave heating was found to be above 90%. The radiochemical purity and physiological distribution of 99mTc-MIBI prepared using lower concentrations of [Cu(MIBI)4]BF4 (up to 200 μg) were found to be comparable to that of 99mTc-MIBI prepared using conventional formulation. The overall study could help in optimizing the microwave procedure for preparation of 99mTc-MIBI and reducing the preparation time from 10 min to 10 s and the amount of [Cu(MIBI)4]BF4 from 1000 to 200 μg. Further studies indicated that the formulations were found to be stable up to 4 h after their preparation. Conclusion: Microwave-assisted radiolabeling can be an alternate route of preparation of 99mTc-MIBI.
| PP44: Off-label use of acetazolamide as decorporating agent of bone-seeking heavy metals: scintigraphic evaluation in animals and human subjects | | |
Gaurav Mittal, Dhruv Nishad, Aseem Bhatnagar, Harish Rawat, Thakuri Singh
Institute of Nuclear Medicine and Allied Sciences, Delhi, India
Background and Objectives: The present study explores potential of acetazolamide (ACZ) for decorporation of bone-seeking heavy metals in animals and human subjects by inducing metabolic acidosis. Materials and Methods: Effect of varying concentration of ACZ on blood pH was studied. Uptake and retention patterns of strontium chloride (SrCl2) and 99mTechnetium-methyl diphosphonate (99mTc-MDP) in the skeletal tissues of ACZ-treated animals were analyzed using atomic absorption spectrometry (AAS) and radiometry, respectively. Battery industry workers and patients undergoing 99mTc-MDP bone scan were recruited to verify the results in humans. Results: ACZ showed a dose-dependent lowering in blood pH of BALB/c mice. There was reduction of 47.53% in strontium uptake into skeletal system in ACZ-treated animals on day-2 as compared to control. Whole-body retention of 99mTc-MDP was 10.66% of initially injected radioactivity in ACZ-treated animals, while it was 34.33% in control. In battery workers, who served as their own controls, significant (P < 0.002) increase of 166% in blood lead level was observed after ACZ treatment as compared to their baseline blood levels, suggesting stimulation of bone resorption activity by ACZ. In a separate study, whole-body 99mTc-MDP burden in patients undergoing bone scan was reduced to 19.5% after ACZ treatment. Reduction in head, lumbar vertebrae, iliac bone, and femur after ACZ treatment was 36.09%, 59.85%, 21.57%, and 38.25%, respectively. An increase of 142.67% in urinary excretion of 99mTc-MDP was further observed in ACZ-treated subjects. Conclusion: Results from animal and human studies indicate potential of ACZ for decorporation of bone-seeking metals and radionuclides.
| PP45: Quality of radiochemical purity in multiple samples of various fractionated cold kits: Testing a cost- and time-effective technique | | |
Meena Negi, Vandana Kumar Dhingra, Manishi L. Narayan
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, India
Background and Objectives: Although indigenous cold kits available from BRIT at nominal rates. Nuclear medicine is an expensive department to run, and it is desirable to reduce costs wherever feasible. Utilizing a cold kit in fractions is one of the most effective ways which does not compromise on quality of imaging if done in a standardized way. We aimed to standardize the cost-effective technique of fractionation. We performed fractionation of the most common three cold kits, i.e., MDP, DTPA, and DMSA(III), on days when patient number was less. We also performed a rapid quality control of these fractions to test for radiochemical purity of the fractions using paper chromatography. Materials and Methods: Samples were taken each of 99mTc-MDP, 99mTc-DTPA, and 99mTc-DMSA-III on various days. All cold kits were fractionated in a standardized manner, i.e., by adding 1 ml normal saline (0.91% NaCl). Each vial was then divided into three fractions of 0.3 ml each in separate vacuum vials and mixed well. Each fraction was labeled and stored in deep freezer. Time required for performing the fractionation was noted. Quality control was performed with a sample of prepared radiopharmaceutical on the day of its use. The radiochemical purity test was done by putting a drop of radiopharmaceutical onto the Whatmann strips and run in different solvents. Solvents used for 99mTc-DTPA and 99mTc-MDP were acetone and saline; however, for 99mTc-DMSA-III acetone was used as solvent. Radiochemical purity was then calculated for each sample. Biodistribution of all samples for quality control was also studied during imaging. Results: Thirty samples of 99mTc-MDP and 10 samples each of 99mTc-DTPA and 99mTc-DMSA III were studied. Radiopharmaceutical biodistribution was found to be appropriate during imaging in all samples. The mean value of radiochemical purity, i.e., labeling yield of 99mTc-MDP, 99mTc-DTPA, and 99mTc-DMSA(III), was calculated as ~95.12%, 91.43%, and 95.68%, respectively. Maximum time in which fractionation procedure completed, i.e., time required for preparing the fraction or thawing, was 10 min. All fractionated aliquots were between 1 and 15 days. Conclusion: Fractionation of cold kits using standardized technique is a time- and cost-effective method and does not influence the labeling efficiency of studied pharmaceuticals. We have used fractionated aliquotes up to 3 days of preparation in patients without any compromise in imaging parameters. Deep frozen fractions could possibly be used up to 15 days in our experience.
| PP46: Standardization of procedure for improved radiolabeling yield of iodine-131-lipiodol | | |
Ravi Seshan, Sanaanjum Sayyad, Sundilla Saraiah, Bikash Tiwari, N. C. Joseph, Shubhangi Mirapurkar, S. S. Sachdev
Radiopharmaceuticals Programme, Board of Radiation and Isotope Technology, Navi Mumbai, Maharashtra, India
Background and Objectives: Iodine-131 (131I)-Lipiodol is a known therapeutic radiopharmaceutical used for the treatment of hepatocellular carcinoma. The treatment involves direct introduction of 131I-lipiodol into hepatic cells via transarterial radioembolization technique maximizing the radiation dose to cancerous cells with minimization of exposure to normal liver. 131I-lipiodol is produced by isotope exchange under inert conditions; however, the radiolabeling yields vary from 60% to 70% generating unlabeled radioiodine (>30%) in volatile form. Such procedures pose radiation risk to the operators/technicians involved in mass scale production of the radiopharmaceutical. Thus, the present work involves standardization of labeling procedure to improve the radiolabeling yields so as to minimize the above losses, making it favorable for producing the radiopharmaceutical in bulk doses. Materials and Methods: Radiolabeling of 131I-lipiodol involves three intermediate steps where initial step involves addition of ethanol (1 mL) to sodium iodide (Na131I; 5–50 mCi; 0.2 mL, pH: 8–10). The pH of the solution was ensured above pH 8.0 by addition of sodium hydroxide solution (pH 8; 0.2 mL). The radioactive ethanolic solution was gently warmed and dried at 45°C under continuous nitrogen purging. After ethanol removal, the residue was re-dissolved in ethanol (1 mL) and lipiodol (2 mL) and resulting solution heated at 80°C for 20 min. Subsequently, the excess ethanol was removed from radiolabeled 131I-lipiodol reaction mixture at 80°C with continuous nitrogen purge to obtain a clear 131I-lipiodol. Above optimized procedure was obtained on optimizing the various experimental conditions, such as temperature, pH, and reaction time. Results: The radiolabeling efficiency obtained was >95% (on measurement of radiolabeled reaction mixture postradiolabeling) and the radiochemical purity of 131I-lipiodol was above 99% as determined by paper chromatography (80% MeOH; Rf 0.0 131I-lipiodol). Initial temperature of 45°C under nitrogen flushing, with maintenance of pH >8 minimized the volatilization of 131I. pH >10 was found to effect degradation of lipiodol with conversion of oil to gel or turbid saponification form. Infrared spectroscopy of the inactive lipiodol-treated under identical labeling conditions showed no degradation of the oil following the above optimized protocol. Conclusions: An optimized radiolabeling protocol of lipiodol with 131I with improved radiolabeling yield was developed following isotopic exchange method, which minimized the radiation risk hazard to the operators involved in production of radiopharmaceutical.
| PP47: Bulk-scale formulation of ready-to-use therapeutic doses of lutetium-177-prostrate-specific membrane antigen-617 at a centralized radiopharmacy setup | | |
Sudipta Chakraborty, K. V. Vimalnath, Rubel Chakravarty, Ashutosh Dash
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Lutetium-177-labeled prostate-specific membrane antigen (PSMA) inhibitor has emerged as a promising modality for targeted therapy of prostate carcinoma. Deployment of ready-to-use formulation of 177Lu-PSMA-617 to nuclear medicine centers from a centralized radiopharmacy setup would facilitate extensive utility of the radiopharmaceutical. The present article reports a detailed systematic study on regular bulk-scale production of ready-to-use doses of 177Lu-PSMA-617 and optimization of storage parameters for its safe deployment to nuclear medicine centers. Materials and Methods: A protocol for regular bulk-scale production of ready-to-use doses of 177Lu-PSMA-617 is developed based on detail and systematic radiochemical investigations. Description of formulation of a typical batch is as follows. To a mixture of 5.0 mL of 0.1 M ammonium acetate buffer (pH ~5) and 0.6 mL of PSMA-617 solution in MilliQ water (0.6 mg, 0.58 μmol) in a sterile container, 1.0 mL of 177LuCl3 solution (37 GBq of 177Lu, 0.28 μmol Lu) in 0.01 M HCl was added. The pH of the resultant mixture was automatically adjusted to ~4.5. The reaction mixture was incubated at ~90°C for 30 min. Subsequently, the reaction mixture was allowed to cool and attain ambient temperature. Thereafter, the contents of the reaction mixture were loaded onto preconditioned C18 Sep-Pak cartridge and the cartridge was washed with 6.0 mL of saline to remove unreacted-free 177Lu. Finally, the 177Lu-labeled product was eluted out in 1.0 mL of absolute ethanol. This was then diluted with sterile normal saline containing gentisic acid (1.0% w/v) (pH ~5) such that the final radioactive concentration of the labeled formulation is 1.11 GBq/mL (30 mCi/mL) with <5% ethanol content. The diluted formulation is then filtered through a 0.22-μm syringe filter. Results: Eight batches of 177Lu-PSMA-617 (40.0 ± 5.5 GBq in each batch) were formulated with radiochemical yield of 95.2% ± 1.3% before its purification. The radiochemical purities of the formulations after their purification and dilution were found to be 99.1% ± 0.2%. In vitro stability studies showed that the formulation retained its radiochemical purity to the extent of >98% up to 4 days postformulation when stored in normal saline containing 1% (w/v) gentisic acid at 4°C with a radioctive concentration of 1.1 GBq/mL. Conclusion: Development of an optimized protocol for bulk-scale formulation of ready-to-use 177Lu-PSMA-617 utilizing moderate-specific activity 177Lu has been successfully accomplished. The reported protocol would be very useful toward facilitating widespread clinical utilization of 177Lu-PSMA-617 in the management of prostate cancer.
| PP48: Development of 99mTc-labeled chitosan-coated magnetic nanoparticles as a promising material for magnetic hyperthermia treatment | | |
Sachin Shetty, Sanjay Bharati, Rajesh Kumar1
Department of Nuclear Medicine, SOAHS, MAHE, 1Department of Oncology and Radiotherapy, MAHE, Manipal, Karnataka, India
Background and Objectives: Magnetic hyperthermia is an emerging approach for cancer treatment. The external high-frequency electric or magnetic field is utilized to increase the temperature of cancerous tissue that results in its destruction. The purpose of the present study was to develop a product that can have imaging as well as treatment capabilities. Materials and Methods: The magnetic nanoparticles were synthesized by coprecipitation method and coated with chitosan. The chitosan-coated magnetic nanoparticles were radiolabeled with Tc-99m using stannous chloride as a reducing agent. The radiolabeling efficiency and cytotoxicity of particles were evaluated. The synthesized particles were characterized for size and morphology using dynamic light scattering, field emission scanning electron microscopy, X-ray diffraction, and Fourier-transform infra-red spectroscopy. Results: The synthesized particles had spherical morphology and were stable till 6 h. The radiolabeling efficiency of chitosan-coated magnetic nanoparticles with Tc-99m was 91.6% ± 1.58%. Conclusion: Chitosan-coated magnetic nanoparticles have shown high radiolabeling efficiency with Tc-99m. The product was biocompatible and could be a promising material for imaging and magnetic hyperthermia treatment.
| PP49: Restructuring of chitosan for the delivery of 32P to hepatoma cells | | |
U. Anushree, Sanjay Bharati1, Rajesh Kumar1
Department of Nuclear Medicine, School of Allied Health Sciences, 1Department of Radiotherapy and Oncology, Kasturba Medical College, MAHE, Manipal, Karnataka, India
Background and Objectives: Therapeutic radionuclides used in the radiation ablation of hepatocellular carcinoma (HCC) face challenges of self-targeting and heterogenous dose distribution. 32P, a potent b emitter with several desirable features of coordination with cellular biomolecules, can easily overcome the challenge of dose distribution. However, a major hurdle in this direction is to effectively deliver 32P into the target tissue. Hence, this study is an attempt to successfully modify chitosan for the delivery of 32P to HCC cells. The study aims to design a polymer–ligand-based system for 32P delivery to hepatoma cells. Materials and Methods: Chitosan was modified through phosphorylation with 85% orthophosphoric acid to form phosphorylated chitosan (PC). PC was then grafted with ligand lactobionic acid to obtain phosphorylated, galactosylated chitosan (P-GC). Phosphorous per gram of the compound was determined spectrophotometrically. Free amino groups of unmodified chitosan and P-GC were qualitatively investigated. Compound was characterized through FTIR. Results: Spectrophotometric tests for phosphorous indicated successful phosphorylation of chitosan. Qualitative test for amino groups revealed the formation of amide bond in the compound. IR spectra of PC and P-GC further confirmed the phosphorylation and grafting of lactobionic acid to the chitosan. Conclusion: 32P-labeled galactosylated chitosan can be synthesized through similar mechanism and aimed to target the hepatocytes.
| PP50: Radiolabeling and scintigraphic evaluation of Tc-99m-labeled 5-fluorouracil and zoledronic acid for tumor imaging | | |
Kan Shekhawat
Bhagwan Mahaveer Cancer Hospital and Research Center, Jaipur, Rajasthan, India
Background and Objectives: In nuclear medicine, the radiation chemistry provides an efficient tool for cancer imaging using compounds labeled with radionuclides that emit gamma radiations. In my presentations, I have to explain the radiolabeling methods of two new compounds (cancer drugs): 5-flurorouracil (5-FU) and zoledronic acid (ZA) for tumor imaging by the scintigraphy. 5-FU is a chemotherapeutic agent and generally used in the targeted therapy for the solid tumors; therefore, I had objective to make this 5-FU a diagnostic compounds for the colon carcinoma, a type of solid tumors, patients. The other drug, ZA, is a bone-seeking bisphosphonate and has a strong affinity to bones, so the target was to do osteoscintigraphy. I have radiolabeled these two anticancer compounds with work horse of nuclear imaging: 99mTc radioisotope. Materials and Methods: For radiolabeling, we have adapted standard reduction methods with slight modifications used for general radiolabeling of radioisotopes. The different concentrations of reducing agents has been used and also standardized for adequate radiolabeling. The chemical analysis of these compounds also has been done before human studies. The previous work regarding the animal and human has been studied. Radiochemistry of the compounds has been studied. We have conducted human studies with these compounds after taking proper human safety. These both radiopharmaceutical injected intravenous and nuclear imaging done with the help of the single photon emission computed tomography system. The other clinical and radiological data also used for the correlations. Radiopharmakinetics and biodistributions have been analysis with the help imaging data and processing software (Syngo, Molecular Imaging). Results: The results of the human studies were very much favorable to make these compounds potential radiopharmaceutical for the Ca colon and bone cancer, respectively. Conclusion: The 5-FU and ZA have provided very satisfactory data and information for to use them as for the nuclear medicine imaging.
| PP51: Radiosynthesis of 68Ga-glutathione radiocomplex and its bioevaluation in experimentally induced colon carcinogenesis | | |
Sumeera Sidiq, Ravi Ranjan, Neelima D. Passi, D. K. Dhawan, Jaya Shukla1, Bhagwant Rai Mittal1, Vijayta D. Chadha
Panjab University, 1Post Graduate Institute of Medical Education and Research, Chandigarh, India
Background and Objectives: The present study describes the computational studies and laboratory radiosynthesis of 68Ga-labeled glutathione (GSH) for its application in detection of cancerous tissues. GSH is the most abundant intracellular low molecular weight thiol. It plays a fundamental role in detoxification and regulates the intracellular redox environment.[1] Elevated GSH levels have been demonstrated in colorectal, lung, breast, ovarian, head and neck neck, and hematologic malignancies;[2] GSH catabolism is mediated by the enzyme gamma-glutamyltranspeptidase(GTT) which is often significantly increased in human tumors.[4] Thus, the radiosynthesis of complex 68Ga-GSH may allow noninvasive diagnosis of cancerous tissue. Materials and Methods: The radiolabeling of radiocomplex 68Ga-GSH was performed by the direct labeling method. Radiochemical purity assay was performed to determine the percentage labeling efficiency of GSH with 68Ga. Analytical and physical measurements such as paper electrophoresis and mass spectroscopy were performed for the characterization of 68Ga-labeled GSH. Colon tumors were developed in healthy male SD rats by giving subcutaneous injections of dimethyhydrazine (DMH) to study the efficacy of the 68Ga-GSH radiocomplex as tumor targeting probe. Molecular docking approach has been used with the aim to computationally simulate the molecular identification process. We have tried to explore the interactions and binding affinities of GSH and its 68Ga-GSH radiocomplex targeting colon tumors by inhibiting GGT. Results: 68Ga-labeled GSH was synthesized within 30 min with a labeling efficiency of 73.5%. Percentage plasma protein binding and log Po/w values for the radiocomplex was found to be 20%–30% and −0.223 ± 0.12, respectively. From the mass spectroscopy results, it was evident that the GSH-68Ga-GSH complex was formed with molecular mass of around 682.64. Biphasic release with slow and fast components as well as high kidney uptake value was observed following intravenous administration of the radiocomplex to both normal and DMH-treated male SD rats. Furthermore, a significantly higher % specific uptake value was observed in colon tumor in comparison to soft tissue. 68Ga-GSH has been well accommodated in the binding pocket of GGT in comparable orientation with lower estimated binding energy −61.08 as compared to the GSH −46.08 with its hydrogen bonding and ionic and hydrophobic interactions. This study shows 68Ga-GSH requires less binding energy as compared to the GSH with an additional charge interaction. Conclusion: The present study presents the radiolabeling of GSH with 68Ga and the specificity of the 68Ga-GSH for the colon tumors.
| PP52: Potential of newly synthesized analog of finasteride “17-oxo-17a-aza-D-homo-5-androsten-3 beta-yl phenoxyacetate” in the diagnosis of prostate carcinogenesis: An experimental study | | |
Gowsia Jan, Vijayta D. Chadha, D. K. Dhawan, Neelima D. Passi
Panjab University, Chandigarh, India
Background and Objective: Considering the 5α-reductase inhibitory activity of the reported oximes and importance of the ester group in increasing the antiandrogenic property, we reasoned to synthesize a compound with general structure having lactam in ring D and esters at 3 β position of androsteron nucleus to be a more potent 5α-reductase inhibitor. The present study radiolabeled the reference drug, finasteride as well as the newly synthesized drug 17-oxo-17a-aza-D-homo-5-androsten-3b-ylphenoxyacetate (17a-aza steroid) with 99mTc and evaluated its target uptake in the prostate of rats. Materials and Methods: 99mTc-finasteride and 99mTc-17a-aza steroid were developed by direct radiolabeling procedure, and the radiochemical purity was assayed by ITLC. For biodistribution studies, the prostate carcinogenesis was initiated by administering testosterone propionate (50 mg/kg body weight), for 21 consecutive days followed by i.p. injections of 100 mg testosterone propionate/kg body weight for 3 days. Subsequently, all the rats received a single i.v. dose (50 mg/kg body weight) of MNU and the animals were dissected after 120 days. The prostate carcinogenesis was confirmed histopathologically and by evaluating prostate-specific antigen levels. The biodistribution studies of both the radiocomplexes were carried in both control and MNU + TP-treated rats to evaluate the percent specific uptake in prostate as a function of time. Results: The radiochemical purities of 17a-aza steroid and finasteride with 99mTc observed were 97% and 93%, respectively, after 30 min of incubation at room temperature. Both radiolabeled drugs were found to be stable for a period of up to 4 h. In Vitro plasma protein binding of 99mTc-finasteride and 99mTc-17a-aza steroid was found to be 83.89% and 95%, respectively. The log Po/w values of 99mTc-finasteride and 99mTc-17a-aza steroid observed were 0.257 and 0.118, depicting slightly lipophilic nature of the radiocomplexes. The maximum percent specific uptake of 99mTc-17a-aza steroid was observed in kidney followed by liver and spleen. The most significant finding of the study was an increase in the uptake of 99mTc-17a-aza steroid in the prostate when compared to the uptake of 99mTc-finasteride. Further, the percent specific uptake of 99mTc-17a-aza steroid was significantly higher in the prostate of carcinogen-treated rats as compared to the prostate of normal control rats. Conclusion: The study concludes that 99mTc-17a-aza steroid possesses better selectivity toward prostate tissue as compared to finasteride and can be explored further for its diagnostic potential in prostate cancer detection and evaluation of treatment response.
| PP53: Homodimeric single photon emission computed tomography agent for amyloid imaging | | |
Garima Mann, Anil K. Mishra, Anupama Datta
DCRS, INMAS DRDO, Brig. S. K. Mazumdar Marg, Delhi, India
Background and Objectives: β-Amyloid plaques are the large insoluble fibrous protein plaques found in the extracellular matrix in the brain. Along with the tau protein, these plaques are hypothesized to be responsible for neutron degeneration and subsequent symptoms of various neuronal diseases. Consequently, imaging of these modalities may aid in pre symptomatic identification of patients at risk of various psychoneurological disorders. From the various molecular imaging modalities available, single photon emission computed tomography (SPECT) has developed as a promising modality owing to on-site production of radionuclide using small generators, making it an appreciable effort in development of feasible imaging techniques. Considering these advantages, there has been a paradigm shift from positron emission tomography to SPECT modality for development of β-amyloid-specific ligands. The work being presented here follows a homodimeric bivalent approach for the design and synthesis of chalcone scaffold-based amyloid-specific ligand. The chelating agent belonging to the “pa” family will be explored for the development of SPECT agent. Chalcone scaffold was selected as the target-specific ligand since it has been reported to bind specifically to β-amyloid plaques and can cross the blood–brain barrier (BBB) easily. Owing to multiple binding sites on β-amyloid aggregates, multivalent ligand may lead to thermodynamically more favorable binding. This would result in improved binding affinity over the corresponding monomer, thereby justifying the bivalent approach. In addition, attachment of dimethyl amino substituted group on para position has also displayed highest binding efficiency over other functionalities. We hypothesize synthesis and application of the as developed bivalent homodimeric molecule to display enhanced binding affinity and BBB penetration. Materials and Methods: The bifunctional chelator was synthesized in three steps: Esterification, partial reduction, and chlorination to form partially chlorinated derivative which was further conjugated with a BOC protected linker. This bifunctional chelator was further conjugated to the chalcone derivative synthesized using substituted benzaldehyde and acetophenone precursors. Results and Conclusion: All the steps were successfully characterized using mass and NMR data. To confirm the hypothesis, the binding potential of the as synthesized ligand with β-amyloid plaques will be studied in vitro followed by extensive in vivo studies to determine uptake in brain and other organs in healthy mice.
| PP54: Production and quality control of copper-64 (64CuCl2) using a Sumitomos's cyclotron and its application as positron emission tomographic imaging agent | | |
Manish Dixit, Nilesh Shankar, Subhash C. Kheruka
SGPGIMS, Lucknow, Uttar Pradesh, India
Background and Objectives: Copper-64 (64Cu) is a useful radiotracer for positron emission tomography (PET) and a promising radiotherapy agent for the treatment of cancer. It has an intermediate half-life (T1/2 12.7 h) and a multiple decay mode that involves b3-, electron capture, and positron decay, these characteristic of 64Cu useful for radiotherapy and for PET monitoring of tumors. Many production routes and processes have been reported to obtain noncarrier-added 64Cu from targets of Ni and Zn. Among them, the 64Ni(p, n)64Cu reaction is a promising route because this reaction can be performed by low-energy protons from a compact cyclotron at a high production yield. We produced the 64Cu via 64Ni(p, n)64Cu using M/s Sumitomo Heavy Industries, Japan's HM-18 cyclotron, and further target material was purified through automatic synthesizer to produced 64Cu as 64CuCl2. Materials and Methods: Highly enriched 64Ni was plated on a gold disk (24 mm in diameter and 2 mm thick) by electrodeposition. 64Cu was produced by bombardment of the 64Ni target in a 18 MeV cyclotron with a 20-μA proton current. After bombardment, 64Cu was separated from the 64Ni target and purified from other contaminants by chromatography using an ion-exchange column. Final activity was eluted with concentrated 1.0M HCl yielding high-specific activity 64Cu as anionic copper chloride. Results: We obtained 64Cu in dried format a yield of 4–5 GBq at the end of bombardment or 40 ± 5 MBq/μA h as the final product and further purification took 3.5 h of processing time. Conclusion: The metallic impurities were a satisfactory low level was obtained by a widely accepted separation using an anion-exchange resin.
| PP55: Optimization of synthesis and quality control of in-house produce [11C]-choline | | |
Priya Saxena, Nilesh Shankar, Manish Dixit, Subhash Chandra Kheruka, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Background and Objectives: Prostate cancer (PC) is the most frequent cancer among men and the third cause of death in economically developed countries. [11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer, especially in early-state prostate cancer diagnostic imaging. Choline is phosphorylated by choline kinase and incorporated into various phospholipids in the body. In certain tissues, including kidney and liver, choline oxidation is prominent. However, imaging with this tracer is a challenging due to the short half-life (20 min) of 11C-radioisotopes and the requirement of its on-site production, making it affordable tracer. This study was focused on the key stages of the synthesis and quality control of [11C]-choline produced. Materials and Methods: In this study, we describe a fast, efficient, and reproducible protocol for the production of 11C-choline in our multipurpose synthesizer (Sumitomo Heavy Industries MPS-100 synthesizer). An automated procedure for the synthesis of 11C-choline is synthesized by 11C-methylation of dimethylethanolamine (DME) in acetone, followed by solid phase extraction of the product on a cation-exchange, CM-cartridge. The cartridge is rinsed with ethanol to remove residual organic impurities before elution of the product with the sterile saline through a sterile filter. Results: The synthesis was completed in approximately 10 min after the end of bombardment with a yield 100 ± 10 mCi with the radiochemical purity of >98%. The synthesized tracers were used for routine patient studies. Conclusion: Details of the automated synthesis technique along with the quality control testing results of the product are presented.
| PP56: Exploring the synthesis of deoxyfluorination reagents and its application to positron emission tomography radiochemistry | | |
Akhilesh K. Singh, Sanjay Gambhir, Manish Dixit
SGPGIMS, Lucknow, Uttar Pradesh, India
Background and Objectives: Organofluorine compounds are featured unique properties that fluorine substitution confers on organic molecules. Notably, in the context of drug design, the Incorporation of carbon−fluorine bonds improves the metabolic stability, solubility, and activity of pharmaceutical chemical entities. Deoxyfluorination of alcohols is one of the most attractive methods for installing aliphatic C−F bonds due to the abundance and accessibility of alcohol-containing precursors. In this technique, a deoxyfluorination reagent generates both an activated leaving group and a nucleophilic fluoride source that react in situ to afford desired product. Fluorine-18 (F-18)-labeling chemistry has developed tremendously over the last decades, but still, new challenging and innovative ways to label the various biological relevant molecules are need of time. We in our laboratory wish to explore such two strategies for nucleophilic insertion of F-18 on to aromatic or aliphatic alcohols. Materials and Methods: We have synthesized these two such prosthetic groups PyFluor (1) and PhenoFluorMix (2) as deoxyfluorinating agent for nucleophilic substitution of aliphatic or aromatic alcohols. Using this strategies, we develop a synthetic protocol to label the couple of known 18F-PET tracers such as [18F]-FDG, [18F]-FLT, and [18F]-FES. Our results are very primarily, and we are exploring to achieve a consistent and reproducible yield and chemistry protocol. This new F-18 chemistry will give us access to explore 18F-labeled clinical and preclinical chemicals entities. Results and Conclusion: We developed a chemistry protocol to synthesis the two prosthetic groups and explored their chemistry to get the deoxyfluorinated chemical entities for clinical and preclinical chemicals studies.
| PP57: Stereotactic intracranial implantation and in vivo bioluminescent imaging of tumor xenografts in athymic mice model system of nucleolipid (DI-C15-ketalized uridine) | | |
Swastika Mishra, A. K. Mishra, Philippe Barthelemy1, Shubhra Chaturvedi
INMAS/DRDO, Delhi, India, 1NSERM U869 and University de Bordeaux, Bordeaux, F-33076, France
Background and Objectives: Innovative therapies are required to stimulate the research in the field of development of brain tumor models in biomedical applications; it requires an exploration due to the complex integrity and peculiar nature of the blood–brain barrier. Therefore, from cell culture to taking to therapeutics or earlier diagnostics for clinical trials, a brain tumor model requires major focus and research. In this piece of research we have tried to stich the major events to be taken care before proceeding for clinical trials in case of brain tumors, we have hereby established xenografts glioblastoma–U87-MG in athymic mice brain through stereotactic surgery and evaluated both functionally and histologically the changes induced in the BBB and endothelial cells and monitored the disruption of BBB during the progression of tumor in the mice brain. Nucleolipids are promising drug delivery systems which allow in vivo tracking using molecular imaging techniques and theranostics agents, especially for brain tumors. Thus, we have evaluated nucleolipid for in vivo tracking by radiolabeling with 99mTc via stereotaxis in mice model. Materials and Methods: The DTPA-NL-DPU (synthesized) using uridine and DTPA (chelating agent) was introduced stereotactically with a depth of 2–3 mm, from the dura matter in the cranium with the tilt of 30 grades of the needle for inoculation of glioblastoma cells U87MG (1 × 105 in 30 μl of cell suspension) for tumor establishment in the athymic mice brain. Tumor was excised, fixed with 4% paraformaldehyde solution, and stored in 70% ethanol. Results: Radiolabeling efficiency of 98% was achieved using 99mTc conferring prolonged systemic circulation and renal route excretion. The biodistribution showed 1.8% ID/g to 2.3% ID/g for intact versus disrupted BBB in mice models. In vivo bioluminescence showed uptake of DTPA-NL-DPU at the tumor site in the brain. Conclusion: Single photon emission computed tomography imaging showed specific uptake (1.8% ID) 15 min p.i of DTPA-NL-DPU at the site of tumor implantation as compared to the other organs except for the liver and kidney showing prolonged uptake due to the lipophilic nature of lipidic conjugate (99mTc DTPA-NL-DPU). The xenogratfts were also studied for their survival analysis; the study provides a powerful and reliable approach for evaluating experimental therapeutic efficacy in animal model.
| PP58: Synthesis and characterization of NOTA-conjugated antimicrobial peptide fragment GF-17 and radiolabeling with 68Ga | | |
Shalini Chopra, Baljinder Singh, Amritjyot Kaur, Anil Kumar Mishra1, Hans-Jürgen Wester2
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 1Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, DRDO, New Delhi, India, 2Department of Pharmaceutical Radiochemistry, Technical University of Munich, Munich, Germany
Background and Objectives: Antimicrobial peptides (AMPs) have a unique property to kill microorganisms and are seen as potential substitute for the conventional antibiotics. As a part of the innate host immunity and unlike antibiotics, bacteria do not develop any resistance against them. GF-17 is an antimicrobial peptide fragment of human cathelicidin LL-37 which is active against both Gram-positive and Gram-negative bacteria. Developing this AMP as a PET probe may be useful to detect active human bacterial infections. The objective of the present study was to synthesize antimicrobial peptide fragment GF-17, its conjugation with bifunctional chelator NOTA, and radiolabeling of the newly synthesized peptide conjugate with gallium-68 (68Ga). Materials and Methods: GF-17 was synthesized by solid phase peptide synthesis using 2-chloro-trityl chloride resin and FMOC protected amino acids. NOTA coupling was done in solution phase in the presence of NHS. Newly synthesized NOTA-GF-17 was purified by HPLC and characterized by ESI-MS. Radiolabeling of NOTA-GF-17 with 68Ga was standardized by varying the peptide conjugate concentration, buffer pH, and reaction time. NOTA-GF-17 (5–30 nmol) was radiolabeled with 68Ga (5 mCi) in 800 μL of sodium acetate buffer (pH = 3–5) by heating at 95°C for different time periods (10, 15, 20, 25, and 30 min). The radiolabeled product was purified by using C8 SPE cartridge and quality control tests were performed. Results: The HPLC data for NOTA-GF-17 demonstrated its retention time, tr = 11.5 min (40%–70% gradient in 20 min). The mass spectroscopy analysis demonstrated the m/z ratios of 1195.0 ([M + 2H]/2) and 797.1 ([M + 3H]/3) corresponding to molecular mass of 2388 Da. The best radiolabeling efficiency (94.33% ± 2.65%) was achieved at a peptide conjugate concentration of 20 nmol, pH of 4, and heating time of 25.0 min. 68Ga-NOTA-GF-17 remained stable up to 2 h. Rf value for 68Ga-NOTA-GF-17 was 0.1 (stationary phase: TLC SG, mobile phase: 0.1 M sodium citrate). 68Ga-NOTA-GF-17 was stable up to 1 h when incubated in human serum at 37°C. In vitro plasma protein binding and lipophilicity for 68Ga-NOTA-GF-17 were 94.59% ± 0.92% (decreased to 89.06% ± 1.44% after 2 h) and −0.18, respectively. Conclusion: A successful radiolabeling of newly synthesized NOTA-GF-17 with 68Ga was achieved. The potential of this radiopharmaceutical for infection imaging requires further preclinical validation before translation to clinical use. Therefore, investigations involving the affinity of NOTA-GF-17 toward different bacterial strains, biodistribution characteristics, and animal PET imaging will be performed in the future.
| PP59: Pharmacoscintigraphic assessment of mucoadhesive nanoparticles designed for colon-specific delivery | | |
Ankur Kaul, Anil Kumar Mishra, Mani Sharma1
INMAS, DRDO, Delhi, India, 1Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, Dehradun, Uttarakhand, India
Background and Objective: Colon-specific delivery of anti-inflammatory drugs is restricted due to numerous reasons such as premature release of the drugs and their enzymatic degradation in the upper gastrointestinal tract. Hence, various nanobased drug delivery systems are being designed to overcome this. The primary objective of this research was to carry out a scintigraphic assessment of drug-loaded mucoadhesive microspheres for colonic delivery. Materials and Methods: The nanoformulation was prepared by optimized concentrations of pectin, ethanol, ethyl acetate, and sodium alginate. This drug-loaded nanoformulation was further characterized for their physiochemical characteristics, such as pH, particle size, and TEM studies, and further, for their in vitro studies including release kinetics and mucodhesive studies. The drug was subjected to prelabeling with 99mTechnetium and further formulated into microspheres. The radiolabeled nanoparticles were then administered to the rabbits in capsule form and gamma scintigraphy was carried out at 1 h and 5 h postadministration. Results: The developed microspheres were found to be spherical in shape which was validated by TEM images. The in vitro studies suggested that the drug release from the formulation was slow and sustained over a period of 5 h. A significant higher drug release was observed in the colonic region in scintigraphic studies postadministration of radiolabeled formulation. Further, the biodistribution studies also validated these findings. Conclusion: The study suggested that the developed formulation has tremendous potential for colonic delivery of drugs in conditions such as inflammatory bowel disease.
| PP60: Gamma scintigraphy evaluation of 99mTc-insulin-loaded microparticles on diabetic rabbits | | |
Shanim Tanwar, Himanshu Ojha, Swarnabha Sarkar, Divya Tripathi, Abhinav Jaimini, Gaurav Mittal, Amit Tyagi
Institute of Nuclear Medicine and Allied Sciences, Delhi, India
Background and Objective: The application of synthetic polymers to medical problems has increased substantially in the last 20 years. The objective of the present work is to evaluate a pH sensitive polymeric formulation with high insulin loading efficiency and sustained and efficient delivery of insulin in the gastrointestinal tract. Materials and Methods: Male New Zealand rabbits weighing 2.5–3.0 kg was provided by experimental animal facility of Institute of Nuclear Medicine and Allied Sciences, Delhi. Diabetes was induced in the experimental rabbits. Animals with glucose levels above ≥300 mg/dl were only used in subsequent studies. Group I: 99mTc-insulin-loaded microparticles filled in gelatin capsule were administered down to esophagous, Group II: 99mTc-Insulin without loading in microparticles was administered down to esophagus using catheter. Gamma camera images of all the animals were taken using at single photon emission computed tomography gamma camera (SPECT, LC 75-005, Siemens, Germany). Results: Radiochemical purity of radiocomplexed insulin was carried out using instant thin layer chromatography silica gel, which was found to be 95%. Gamma camera imaging of all the animals was carried out at different time interval (30 min, 2 h, and 4 h). Control animal fed with 99mTc-insulin showed diffusion of radioactivity into the body tissues within 30 min of oral administration. After 4 h, almost all the radioactivity was diffused into the surrounding tissue. The second group of animals fed with the 99mTc-insulin loaded into the poly(PEGDMA4000-MAA) microparticles showed the concentration of activity into the stomach after 30 min of oral administration, while negligible activity was observed into the surrounding tissues. While after 4 h, significantly higher diffusion into the tissue such as palm, hands, and other visceral organs of animal body was observed, while the activity was also observed in the stomach and intestine. Oral administration of 60 I.U./kg insulin dose loaded in poly(PEGDMA4000:MAA) microparticles and poly(PEGDMA2000:MAA) microparticles showed almost similar effect and reduced the fasted blood glucose level by 78% within first 2.5 h of the treatment and maintain the same for the next 3.5 h and then slowly rose and approached the control value within the next 2 h. Conclusion: Radiometric studies confirm sustained and pH sensitive behavior of poly(PEGDMA4000-MAA)-based microparticles. The developed polymeric carrier has shown the ability to control blood glucose level to normal level up to 8 h in case of diabetic rabbits.
| PV42: Comparison between manual labeling of gallium-68-DOTA NOC with ITG and ithemba generator: A preliminary study | | |
K. M. Kavyasree, Ajit Shinto1, S. Arun Pandiyan1, E. R. Radhakrishnan1, V. J. Arnold1, F. R. Kingsley1, Raghi P. Jose1, B. Surya1, K. K. Kamaleswaran1
Kovai Medical Centre Research and Educational Trust, 1Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
Background and Objectives: Gallium-68 DOTA NOC binds to the somatostatin receptors that are seen on the surface of neuroendocrine tumor. There are two methods of labeling DOTA NOC. In this study, we compared the manual labeling of 68Ga-DOTA NOC with ITG and ithemba generator types. Materials and Methods: A total of 40 samples were used to compare the radiochemical purity of the manual labeling of 68Ga-DOTA NOC with ITG and ithemba generator types. The required materials are Ge-68-Ga-68 generator, solvents such as 0.5 M HCl. Manual labeling was done as follows: Ga-68 is eluted from the ithemba generator using 4 ml of 0.6 M HCL in fraction method directly to clean vial. HEPES buffer is transferred to the reaction vial to adjust pH. The vial is sealed with aluminum cap and mixed well. The vial is incubated at 90°C in a water bath for 10 min. It is allowed to cool for few minutes. Ga-68 is eluted from the ITG generator using 4 ml of 0.6 M HCL directly to clean vial. Sodium acetate buffer is transferred to the reaction vial to adjust pH. The vial is sealed with aluminum cap and mixed well. The vial is incubated at 90°C in a water bath for 10 min. The radiochemical purity of 68Ga DOTA NOC was determined by instant thin layer chromatography silica gel (ITLC SG) as stationary phase and acetonitrile:water 1:1 as a mobile phase. The procedure is done by adding a point source of the radiopharmaceutical in an ITLC SG strip. The strip is then kept immersed in the respective solvent in a test tube, and it is kept undisturbed until the solvent reaches the desired mark in the strip. Then, the strip is dried completely and the upper and lower zone is separated and was analyzed by well counter. Results: Average radiochemical purity of manual labeling of ITG generator and ithemba generator was 96.02% ± 0.54% and 97.81% ± 0.32%, respectively. There is no statistical difference between radiochemical purity of manual labeling and two generator types (P > 0.05). Conclusion: Our study suggests that there was no significance difference between radiochemical purity of manual labeling and two generator types. Moreover, ithemba generator gives better radiochemical purity.
| PV43: Comparison between manual labeling of 68Ga-prostrate-specific membrane antigen with ITG and ithemba generator: A preliminary study | | |
S. Srividhya, Ajit S. Shinto1, S. Arun Pandian1, V. J. Arnold1, E. R. Radhakrishnan1, F. R. Kingsley1, Raghi P. Jose1, B. Surya1, K. K. Kamaleswaran1
Kovai Medical Centre Research and Educational Trust, 1Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
Background and Objectives: Ga68 prostate-specific membrane antigen (PSMA) is radiopharmaceutical used for prostate cancer. The preparation is done using two types of generator – ITG and ithemba generator. Nowadays, ITG is mostly used for preparation. An ithemba generator is compared with ITG generators for labeling PSMA with Ga68. In this study, we compared the manual labeling of 68Ga-PSMA with ITG and ithemba generator types. Materials and Methods: A total of 40 samples were used to compare the radiochemical purity of the manual labeling of 68Ga-PSMA with ITG and ithemba generator types. The radiochemical purity is done for Ga68-PSMA produced by both generators. Ga-68 is eluted from the ithemba generator by the following steps, 4 ml of 0.6 M HCL in fraction method directly to reaction vial. HEPES buffer is transferred to the reaction vial to adjust pH 4–4.5. The vial is sealed with aluminum cap and mixed well. The vial is incubated at 90°C in a water bath for 10 min. It is allowed to cool for few minutes and quality control is carried out. Ga-68 that is eluted from the ITG generator has following procedures, using 4 ml of 0.05 M HCL in directly to reaction vial. Sodium acetate buffer is transferred to the reaction vial to adjust pH 4–4.5. The vial is sealed with aluminum cap and mixed well. The vial is incubated at 90°C in a water bath for 10 min. It is allowed to cool for few minutes. Radiochemical Purity Test: The radiochemical purity of 68Ga-PSMA was determined by instant thin layer chromatography silica gel (ITLC SG) as stationary phase and acetonitrile:water 1:1 as a mobile phase. The procedure is done by adding a point source of the radiopharmaceutical in ITLC SG strip. The strip is then kept immersed in the respective solvent in a test-tube, and it is kept undisturbed until the solvent reaches the desired mark in the strip. Then, the strip is dried completely and the upper and lower zone is separated and strips were analyzed by well counter. Results: Average radiochemical purity of manual labeling of ITG generator and ithemba generator was 95.02% ± 0.44% and 96.81% ± 0.33%, respectively. There is no statistical difference between radiochemical purity of manual labeling and two generator types (P > 0.05). Conclusion: Our study suggests that there was no significance difference between radiochemical purity of manual labeling and two generator types. Moreover, ithemba generator gives better radiochemical purity.
| PV44: Validation of an in vivo technique for quality assessment of 99mTc-HSA nanocolloid kit and its shelf-life extension | | |
Krishna Mohan Repaka, Krishna Mohan Repaka, Suresh Subramanian1, Usha Pandey2, Aruna Korde1
Board of Radiation and Isotope Technology, Delhi, India, 1Division of Radiopharmaceuticals, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Particle size distribution (PSD) followed by % radiochemical purity (%RCP) assessment is the currently employed quality control (QC) measure to assess suitability of HSA-nanocolloid kit used in SLN detection. However, it would be advantageous to have a standby protocol in case of breakdown or unavailability of PSD measurement. Therefore, we validated (as per the Radiopharmaceuticals Committee [RPC] guidelines) a previously reported footpad method in rat model, which is based on physiological distribution (PD) studies of the formulation, as an alternate QC protocol. Furthermore, the current shelf-life of this product supplied from BRIT is only 2 months thereby limiting its convenience at both manufacturers as well as at user end. Using this method to complement existing QC protocol, investigations were conducted to ascertain the possibility of increasing shelf-life of this kit. Materials and Methods: HSA nanocolloid kit was labeled with 10 mCi (1 ml) of 99mTcO-4. PD studies were performed in normal adult Wistar rat (n = 3). The formulation (50 μl) was administered subcutaneously into the footpad postanesthesia, followed by gentle massage of footpad region to facilitate draining of the preparation into proximal lymph nodes. At the end of 2 h incubation period, the animals were administered under anesthesia in identical fashion with patent blue dye and sacrificed 5 min later. Activity in the proximal nodes was measured and popliteal extraction (PE) was calculated. Further, physicochemical evaluations and biological tests were carried out every month for up to 5 months from the date of production as per the RPC monograph. Six consecutive batches of this product were employed in this study to establish the stability of this product. Results: Our PD studies have demonstrated ≥80% PE reproducibly for all the batches tested and are in compliance with the existing RPC specifications, thus validating this technique as an alternate QC method. In our shelf-life investigations, it was observed that the appearance of the kit formulations were translucent and colorless, pH was between 5.5 and 6.5, and RCP was above 95% till 5 months for all the six batches. The sterility, bacterial endotoxin levels, and PSDs were also in compliance with the RPC guidelines. Conclusion: PD studies have been validated as an alternate QC method to particle size distribution of HSA-nanocolloid kit used in SLN detection. Based on our stability studies, the shelf-life of the kit has been extended to 4 months. Both of them have been approved by RPC.
[TAG:2]PV46: Rhenium-188 hydroxyethane 1,1-diphosphonic acid for bone pain palliation using Bhabha Atomic Research Centre-hydroxyethane 1,1-diphosphonic acid kits versus pars-hydroxyethane 1,1-diphosphonic acid kits: A comparison on preparation and performance aspects at hospital radiopharmacy[/TAG:2]
Kingston Ajay, Ajit S. Shinto1, E. R. Radhakrishnan1, S. Arun Pandiyan1, V. J. Arnold1, K. K. Kamaleswaran1, F. R. Kingsley1, Raghi P. Jose1, B. Surya1
Kovai Medical Center Research and Educational Trust, 1Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
Background and Objectives: Bone metastases occur as result of a complex of pathophysiological process between host and tumor cells. Initially, 153Sm and 177Lu was used, but nowadays, 188Re-hydroxyethane 1,1-diphosphonic acid (HEDP) is used to treat bone pain palliation because of its short half-life of 16.8 h. It has gamma energy of −150 Kev and beta energy of −2.11 Mev that is optimum for therapy and gives better result than others. Recently, the Bhabha Atomic Research Centre (BARC) had developed a freeze-dried kit for the preparation of rhenium-188 HEDP. The present study compares the radiochemistry aspects of indigenous BARC-HEDP kits with commercially available HEDP kits from Pars Isotope Company, Iran. Materials and Methods: Freeze-dried HEDP kits were obtained from Radiopharmaceuticals Division, BARC, and Pars Isotope Company, Iran. Following recommended procedures, rhenium-188 HEDP was prepared using freeze-dried kits from both sources using freshly eluted rhenium-188 sodium perrhenate obtained from commercial tungsten-188/rhenium-188 generator. Results: Both kits could be used for the preparation of rhenium-188 HEDP in >95% radiochemical purity. Rhenium-188 HEDP prepared from both kits showed comparable in vitro stability as well as pharmacokinetic properties. The normal bone-to-soft tissue ratio observed for rhenium-188 HEDP prepared using BARC HEDP kit and Pars HEDP kit was 1.993 and 1.416, respectively. Conclusions: Both HEDP kits provided a user-friendly solution for the preparation of rhenium-188 HEDP. While Pars HEDP kit permits the addition of only 2 mL of rhenium-188 perrhenate solution per kit vial, BARC HEDP kit allows up to 5 mL. This feature permits the preparation of patient dose of rhenium-188 HEDP even with older generators providing rhenium-188 perrhenate having a low radioactive concentration (activity/mL). In addition, availability of an indigenous product is always preferable over imported options.
| PV47: Synthesis optimization of 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole, beta-amyloid positron emission tomography imaging tracer via in-house synthesized precursors | | |
Nilesh Shankar, Sanjay Gambhir, Manish Dixit, Akhilesh K. Singh, Chand P. Sharma, Atul Goel1
SGPGIMS, 1CDRI, Lucknow, Uttar Pradesh, India
Background and Objectives: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder characterized by irreversible memory impairment, continuous cognitive decline, and behavioral disturbances. AD causes about two-thirds of dementia in the elderly. It is estimated that by 2050, there will be 13.2 million cases of AD in the US. At present, there is no medical treatment that cures or prevents AD. The production and accumulation of b-amyloid peptides (Ab) is believed to be pivotal to the pathogenesis and progression of AD, and therefore, research on the treatment of AD has focused on the anti-amyloid therapies. It is well documented that the formation of Ab plaques precedes the appearance of clinical symptoms. We synthesized precursors for 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole (11C-PIB) and subsequent labeling to produce labeled 11C-PIB via fully automated route. Materials and Methods: In this study, we describe the synthetic route for the synthesis of arylbenzothiazoles derivatives to be used as precursors. These precursor were further labeled with [11C]-radioisotope via two synthetic strategies either [11C]-methyl iodide route or [11C]-methyl triflate route using fully automated synthetic module. All quality control tests were performed for being used as clinical product as positron emission tomographic imaging agents. Results and Conclusion: The overall radiochemical yield was good with the labeling purity is more than 96%. The reproducibility of this automated synthesis module is very high.
| PV48: Synthesis and purification of 5,7-Bis(2-fluoro-ethoxy)-chrysin: A potential positron emission tomographic tracer for breast tumor | | |
Somnath Kar, Sharmila Banerjee, N. Lakshminarayanan, Suttapa Rakshit, Yogita Pawar, S. G. Mohite
Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background and Objectives: Chrysin is a natural flavonoid and a well-known aromatase inhibitor. Aromatase catalyzes the final and rate limiting step during the biosynthesis of estrogen from androstenedione. Aromatase enzyme is overexpressed in a wide range of breast tumors. Our objective is to radiolabeled chrysin with [18F]fluorine and evaluate its potential as a breast tumor imaging agent. The present study reports the radio synthesis, purification, and in vitro cell-binding study of chrysin. Materials and Methods: All the chemicals were purchased from Sigma-Aldrich. 18F-Fuoride production and radiosynthesis were performed using GE PETtrace cyclotron and GE TRACERlab module (Configured for 2-[18F]FDG production), respectively. [18F] radiofluorination was carried out using dry [18F] tetrabutylammonium fluoride. The radiosynthesis was carried out by a one-pot two-step process. In the first step, fluoroethyl tosylate was synthesized by fluorination of ethylene ditosylate. In the second step, fluoroethyl tosylate was tagged with chrysin to form fluoroethylchrysin. The reaction mixture was purified using 4 g neutral alumina. The final product was eluted from the column with 10% ethanol. Positron emission tomography/computed tomography (PET-CT) imaging in normal rabbit was conducted to see the uptake pattern and clearance of the radiolabeled compound. Results: The reaction conditions were optimized to obtain maximum yield. Radio-TLC and radio-HPLC analysis of the final product showed greater than 95% purity. A bed volume of 4 g neutral alumina was found to be sufficient for efficient purification. A nondecay corrected radiochemical yield of 40% (n = 3) was obtained with the reaction time of 60 min. PET/CT studies with normal rabbit showed uptake in the brain and bone marrow, with no significant uptake in bones and rapid clearance from the whole body within 2 h via renal route. Conclusion: [18F]Fluoroethyl chrysin was successfully synthesized and purified. The radiochemical yield with a reaction time of 60 min was found to be 40% (nondecay corrected) and a radiochemical purity of 95%. The radiotracer showed sufficient in vivo stability as there was no bone uptake up to 4 h postinjection. Further studies in in vitro systems and biodistribution studies with animal models are in progress.
| PV49: In-house radiosynthesis of various [18F]-labeled positron emission tomography tracers for clinical use: our initial experience | | |
Sunil Kumar
DSCI, Delhi, India
Background and Objectives: [18F]-labeled radiotracers have shown clinical usefulness in oncology, cardiology, and neurology. Half-life of [18F], i.e., 109.7 min, makex it more feasible for distribution of [18F]-labeled radiotracers to long-distance positron emission tomographic (PET) centers. The study aims to synthesize batch production of various [18F]-labeled radiotracers in automated synthesizer module for in-house clinical use. Materials and Methods: [18F]-labeled radiotracers were produced in GE TRACERlab FX2 N Module. Enriched O-18 water (2.5 ml) was bombarded in niobium target in GE PETtrace 860 cyclotron via [18O (p, n) 18F] for 55 min at 45 μA and produced around 2.7Ci of [18F] EOB. Precursor mannose triflate was used for labeling with [18F] in the synthesis of [18F]-FDG following alkaline hydrolysis and finally [18F]-FDG produced. Precursor TET was used for labeling with [18F] in the synthesis of [18F]-FET following acidic hydrolysis and finally [18F]-FET produced. Precursor 3-N-Boc-thymidine was used for labeling with [18F] in the synthesis of [18F]-FLT following alkaline hydrolysis and finally [18F]-FLT produced. Radiotracers produced were passed through conditioned SPE cartridge for purification and final product was transferred into a sterile vial through 0.22 μm sterile filter and a small volume was sent for quality control testing. Synthesis of FDG, FET, and FLT was done via SN2 reaction and it took around 40 min, respectively. Results: Average yield of [18F]-FDG was 42% ± 5%, n = 260 in the duration of 14 months. Total [18F]-FDG produced = 16.9 Ci which is sufficient to scan 4100 patients. [18F]-FDG batches failed = 11, due to degraded mannose triflate in a single lot. Average yield of [18F]-FET was 30% ± 5%, n = 3 in the duration of 14 months. Total [18F]-FET produced = 2.3Ci which is sufficient to scan 10 patients. Average yield of [18F]-FLT was 10% ± 5%, n = 2 in the duration of 14 months. Total [18F]-FLT produced = 240 mCi which is sufficient to scan 10 patients. Conclusion: [18F]-labeled radiotracers have been successfully synthesized in short time with high radiochemical yield and purity. Till date, more than 4120 different kind of cancer patients have undergone PET scan from these radiotracers at our center.
| PV50: 68Ga-labeled radiopharmaceuticals by an automated/manual module | | |
Rajeev Kumar, Madhavi Tripathi, N. A. Damle, C. S. Bal
All India Institute of Medical Sciences, Delhi, India
Background and Objectives: We routinely synthesize 68Ga-labeled compound for positron emission tomography (PET) at our center. The aim of the present study is to share our experience regarding the routine synthesis and quality control of generator-based 68Ga-labeled radiopharmaceuticals using an automated/manual module. Materials and Methods: 68Ge/68Ga generator (Isotope Technology Garching GMBH ITG, Germany) containing 50 mCi was eluted with 4 ml of 0.05M HCl. Elution yield is (≤80%) and its chemical form is [68Ga] GaCl3 in 0.05 HCl. This eluant was passed through a cation exchange, strata X-C (phenomenex), to reaction vessels or direct in to reaction vessels. The reaction vial contained precursor dissolved in buffer solution. The reaction vessel was heated at a certain temperature. The total heating time depended upon the precursor. Once heating was completed, it was cooled and diluted by adding 3 ml metal free water. Now, the product was transferred in to the cartridge for purification. From this, cartridge product was transferred in to product vial with the help of a solution containing mixture of ethanol and metal-free water (1:1 ratio). Product was passed through 0.22 μm filter. The product was diluted by adding 10 ml normal saline. All the synthesis steps were carried out in automated module (Modular Lab, Eckert and Ziegler, Germany and Gallium Synthesizer PET radiopharmaceuticals, India). The total synthesis time depends upon precursor. During the whole procedure, the radiation level was monitored around the module every 3 min. Quality control test (Clarity, pH, and radiochemical purity) was performed. Stability was also checked by running chromatograms immediately after the preparation and later at 1, 2, 3, and 4 h. Results: The maximum yield of 68Ga was approximately 70%. The product was carrier-free (without 68Ge). The labeled preparation was clear with pH around 6.0. 68Ga-radiopharmaceuticals conjugate was prepared with very high chemical purity (≤99%). There was no free 68Ga. The product was stable for 4 h. The whole assembly was kept in hot cell. Hence, outside the hot cell, the radiation level was near-background level during synthesis. Conclusion: It is possible to synthesize generator-based PET radiotracer 68Ga-radiopharmaceuticals with high radiochemical purity and good stability using automated module. It is safe from the radiation safety aspect also.
| PV51: Manual labeling of Ga68 radiopharmaceuticals and evaluation of radiochemical purity by two different methods | | |
E. R. Radhakrishnan, Arun Pandiyan, Ajit S. Shinto, Raghi P. Jose, K. K. Kamaleswaran
Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
Background and Objectives: Ge68-Ga68 generator produces positron emitting isotope Ga68 from a source of decaying Ge68. Ga68 is routinely labeled to the pharmaceutical molecules DOTANOC for neuroendocrine tumor (NET) and prostate-specific membrane antigen (PSMA) for prostate cancer. Radiochemical purity (RCP) was evaluated by paper chromatography technique. ITLC-SG paper was used as a stationary phase and aetonitrile:water (1:1) and ammonium acetate:methanol as a mobile phase. Sep-Pak plus cartridges are used for filtration if radiopharmaceutical (RP) fails, by passing the radiolabeled complex through the cartridge in which the free gallium stays in the filter. The study aims to check the labeling efficiency and RCP of gallium RPs by the manual method. Materials and Methods: Fractional elution of Ge68-Ga68 generator was done as per the protocol in ithemba and ITG generator. In ithemba generator, eluent used was 0.6 M HCL and HEPES buffer to adjust the pH of the preparation. In ITG generator, eluent used was 0.05 M HCL and 0.25 M sodium acetate buffer to adjust the pH of the preparation. Ga68 RPs were prepared using 10 μg for PSMA and 35 μg for DOTANOC as ligands. Buffer was added to get pH of 3.5–4.5. Boiled for 10 min and RCP was found using ITLC paper as static phase and acetonitrile:water and ammonium acetate:methanol as mobile phase in a paper chromatogram. Results: By comparing the quality control of Ga RPs done shows that ammonium acetate:methanol RCP method shows better accuracy comparing to acetonitrile:water method. Conclusion: In our experience, calculated RCP% of Ga RPs using both acetonitrile:water (1:1) and ammonium acetate:methanol as mobile phase showed a more accurate representation of RCP for prepared products. If both the quality control tests for a preparation were more than 90%, then only the RP should be injected to patient. Ammonium acetate and methanol has a good accuracy to calculate the %RCP compared to acetonitrile and water as a mobile phase. The radiation exposure measured in a pocket dosimeter after the Ga RP preparation was found to be 2–3 μS, which is within the ALARA limit.
| PV52: Bacterial endotoxin test an alternate method for pyrogen test for 99mTechnetium cold kits | | |
Geetha Rajagopalan, Seema Syed
Board of Radiation and Isotope Technology, India
Background and Objectives: The aim of our work was to analyze endotoxins in 99mTechnetium (99mTc) cold kits (TCK-injectables) and to replace pyrogen test (PT) with bacterial endotoxin test (BET). Endotoxins represent the pyrogens (fever-inducing agents) of Gram-negative bacteria. Testing of endotoxins is very important for any injectables. TCKs were outsourced for PT in rabbits to FDA-approved laboratory. The disadvantage of this test is that it is time-consuming, is expensive, and cannot be used to test certain drugs that depress the fever. Maintenance of rabbits is cumbersome and very few labs undertake this test. BET is a simple in vitro test, which is based on the reaction of endotoxin with protein (lysate) from amoebocyte of horse shoe crab forming turbidity, precipitation or a gel clot. Materials and Methods: LAL reagents: control endotoxin, and lysate (sensitivity 0.125 EU/ml), LAL reagent water (LRW), 0.9% saline, 60 mM CaCl2, 9.6 mM Ca++ and Mg++ free phosphate buffer saline, BRIT TCKs, heating block. We have standardized 12 99mTc kits of BRIT using gel-clot technique for BET, approved by RPC. We have analyzed in-house about 90 kits by gel-clot technique and correlation studies with PT showed 100% correlation. We have also attempted to develop BET for some of new TCKs such as macroaggregated albumin (MAA), ubiquicidine, human serum albumin (HSA) nanocolloid, TRODAT, and HYNIC-TOC. The maximum valid dilution was standardized at 200 and endotoxin limit was not more than 25 EU/ml. In some kits, viz., sulfur colloid, MAA, and HSA nanocolloid false results were observed due the presence of particles, which was resolved by filtering through 0.22 μm polyethersulfone membrane. In certain kits, viz., glucoheptonate and TRODAT, PBS was used as diluting agent instead of LRW to avoid false-positive. High amount of cation concentrations causes aggregation resulting in a pseudocoagulation reaction giving rise to false positive. In some kits, CaCl2 was added to overcome inhibition observed in the test. Conclusion: BET is a more simple, sensitive, reliable, and easy to perform compared to PT. We have replaced PT with BET which is an better alternate method.
| PV53: Development and evaluation of acute lung injury using noninvasive gamma scintigraphy | | |
Divya Tripathi, Amit Tyagi, Swarnabha Sarkar, Harish Rawat1, Lalita Mehra1, Thakuri Singh, Abhinav Jaimini1, Gaurav Mittal
Departments of Combat Sciences and 1Nuclear Medicine, INMAS, DRDO, Delhi, India
Background and Objectives: Animal model of acute lung injuries is helpful to simulate the humans. Acid aspiration-induced lung injury is one of the validated methods to induce acute respiratory distress syndrome (ARDS). The effect of acid instillation on the pulmonary endothelial barrier has been extensively studied. 99mTc MAA radiotracer is frequently used as a lung imaging agent, which is radiolabeled, precipitated, biodegradable macroaggregated of human serum albumin used in the evaluation of pulmonary perfusion. Materials and Methods: There are several methods which can cause acute lung injuries out of them acid-induced lung injury method used for the creation of ARDS. Briefly, the instillate was prepared using 0.1 N HCl (pH 1.5) in 1/3 normal saline to match the osmolality of gastric aspirates. Three White New Zealand rabbits were administered 3 ml of 0.1 N HCl injected directly into the right lung through intrathoracic injection. Similarly, control group animals were injected with equal amount of saline into the right lung. After 3 days of lung injury, animals were administered with 3 mCi of lung-specific 99mTc MAA tracer intravenously for evaluation of the lung infusion. After 15 min of 99mTc MAA administered, images were acquired at 500 K counts for 30 min followed by single photon emission computed tomography (SPECT)-CT. The counts obtained from the images were evaluated. Results: It was observed in the SPECT-CT image that animals injected with 0.1 N HCl showed higher accumulation of the MAA-99mTc in the acid-injected area. Region of interest was drawn which revealed that acid-infused right lungs have 66% ± 3% more accumulation of radiotracer in comparison to 34% ± 3% in the left lungs. While in case of control group animals, no significant difference was observed in the accumulation of radiotracer in the left and right lungs. The nonsymmetric accumulation of radiotracer in the control and acid-infused lungs is associated with the inflammation induced due to acid perfusion. It is evident from the MAA-99mTc SPECT-CT scan can be used for evaluation of acute lung injury mode. Conclusion: As it is well established that acid causes severe lung injuries and acute lung injury produced by instilling diluted acid into the lungs, concentration of the acid determines the severity of injury which were correlative to the 99mTc MAA scintigraphy results, indicating the accumulation of the radiotracer specifically into the acid-infused lungs only due to increased blood flow to local inflammation.
| PV54: Decontamination study of radionuclide contamination using topical formulation and evaluation using gamma scintigraphy | | |
Swarnabha Sarkar, Amit Tyagi, Divya Tripathi, Harish Rawat1, Lalita Mehra, Abhinav Jaimini1, Gaurav Mittal
Departments of Combat Sciences and 1Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India
Background and Objective: With the increased use of radionuclides and metals in the warfront, there has been an increase in the acute and chronic toxicity in the exposed combatant. Therefore, it is essential to reduce radionuclide/metal contamination using nontoxic decontaminating agents as a part of prehospital treatment under combat casualty management. The aim of the study is to evaluate the decontamination potential of topical radionuclide exposure at the wound site using the developed topical formulation. Materials and Methods: Adult female Sprague–Dawley rats were obtained from the experimental animal facility of Institute of Nuclear Medicine and Allied Sciences, Delhi. The rats were shaved on the dorsum before conduction of the experiment; thereafter, circular excision wounds were created on the shaved skin surfaces and the rats were housed in individual cages. 99mTc sodium pertechnetate in saline was administered at the wound site of all the rats. They were grouped into four groups, i.e., control, test 1 (INM01), test 2 (INM02), and test 3 (INM03) comprising six animals in each group. Equal weight of all the formulations, i.e., INM01, INM02, and INM03, was applied on the wound site after 10 min of 99mTc application on the wound site. The animals were maintained at 12-h day/night cycle and controlled temperature conditions. Food and drinking water were provided ad libitum. Results: After the completion of the experimental procedure, the animals were subjected to gamma scintigraphy. Each image was acquired from the dorsal view for 3 min. Separate regions of interest were drawn around the whole body and at the wound site. The percentage retention for pertechnetate in all the experimental groups was calculated. The percentage retention of control (5 min: 75.06%, 6 h: 25%, 24 h: 22.95%), INM01 (5 min: 84.06%, 6 h: 39.87%, 24 h: 30.07%), INM02 (5 min: 84.88%, 6 h: 35.52%, 24 h: 23.80%), and INM03 (5 min: 86.64%, 6 h: 57.43%, 24 h: 43.73%). The results indicate that the developed formulation (INM03) showed maximum retention potential (43.73%) at 24 h in comparison to the other groups (control: 22.95%, INM01: 30.07%, and INM02: 23.80%). Conclusion: The developed formulation INM03 shows the most efficient retention potential of pertechnetate, suggesting the presence of chemically active sites in the developed formulation which serves as the coordination sites for the radionuclides/metals which may play a role in reducing the contamination from dispersing into the circulation.
| PV55: Radiolabeling of Ensure, a food supplement, with Tc-99m and optimization of scintigraphy protocol for liquid gastric emptying time | | |
Monika Hooda, Priya Bhusari, Jaya Shukla, Bhagwant Rai Mittal
Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India
Background and Objectives: Gastric emptying scintigraphy using radiolabeled solid meal (Tc-99m-sulfur colloid-IDLI) is considered as the best method to diagnose delayed gastric emptying. Radiolabeled liquid meal emptying studies have also been employed using Tc-99m/111I-DTPA to diagnose gastric emptying although it is less sensitive but holds importance for patients who cannot tolerate solids. Hence, the present study aimed at radiolabeling the nutrient supplement solution (Ensure) as a tracer for studying the liquid emptying time in patients with dyspepsia and gastroparesis. The study aims to standardize the labeling procedure of 99mTc-Ensure and perform it quality control and evaluate the final labeled product as a potential clinical product for liquid gastric emptying study. Materials and Methods: 99mTc was labeled with nutrient supplement (Ensure) by direct radiolabeling procedure using stannous chloride reduction method. Variable concentrations (1, 2, 5, and 10 mg) of Ensure was dissolved in 500 μL of water and centrifuged at 3000 rpm for 10 min. 100 ul of the supernatant was dissolved in variable concentration (10, 20, 30, 40, and 50 μg of SnCl2.H2O in (0.1, 0.025, 0.05 M HCL in mg/mL) of the prepared stock solution. Incubation was done at room temperature for 30 min and centrifuged at 3000 rpm for 10 min. The pellet and supernatant were separated. The radio-ITLC of supernatant and pellet was performed to check for radiolabeling efficiency. A total of seven patients (4 males:3 females) with a mean age of 50 years were included. The liquid diet was prepared by mixing 60 g of Ensure in 400 mL water. 1.5–2 mCi 99mTc-labeled-Ensure to it. The liquid emptying study was performed on dual headed gamma camera (Symbia T16, Siemens and Infinia Haweye, GE). Results: 20 μg of SnCl2.H2O was found as optimum quantity to reduce 99mTc to be able to bind to ensure. The radiolabeling efficiency (~75%) was found consistent even after increasing the concentration of ensure to 10 mg. Further, the morality of HCL was varied and maximum radiolabeling yield (>90%) was obtained with 0.01 M HCl. Further, the labeled product was again centrifuged and the pallet component had maximum activity. Hence, using the pallet component made this as clinical usual product with radiolabeling efficacy of >95%. Conclusion: 99mTc-Ensure can be labeled in-house with good labeling efficiency, and it demonstrates in vivo stability for up to 2 h with no free 99mTc localization in the thyroid gland, salivary glands in any of the patients. Hence, 99mTc-Ensure can be used as a potential liquid meal in gastric emptying studies.
| PV56: Sustained release of thallium-201 from poly(hydroxymethacrylate) hydrogel device | | |
Tarpan Gupta, Chandra Shekhar Beniwal, Divya Tripathi, Swarnabha Sarkar, Harish Rawat1, Abhinav Jaimini1, Gaurav Mittal, Amit Tyagi
Departments of Combat Sciences and 1Nuclear Medicine, INMAS, DRDO, Delhi, India
Background and Objectives: Development of a sustained drug delivery device based on polymeric hydrogels is advantageous by means of their biocompatibility and mimics biological nature. Poly(hydroxymethacrylate) (poly[HEMA]) is an FDA-approved polymer for various applications. The present study evaluates poly(HEMA) hydrogel devices for sustained release of thallium-201 as a model compound. Materials and Methods: Thallium-201 was taken as a model compound to see the release profile from various poly(HEMA) hydrogel devices crosslinked with different percentage of EGDMA. Two hundred micro-Curie of activity was loaded in various poly(HEMA) hydrogel devices separately and the open end of the hydrogel device was sealed using cynoacrylate adhesive. Hydrogel devices were kept in 20 ml of saline water (0.9 N NaCl solution) as surrounding media. Hydrogel devices were taken out and the activity released into the surrounding media was checked at fixed time interval using gamma counter (Electronics Corporation India Limited, ECIL). Results: In vitro release of thallium-201 from poly(HEMA) hydrogel device synthesized using different EGDMA percentage showed sustained release of thallium. Hydrogel devices synthesized using 1% of EGDMA as cross-linker showed approximately 50% of activity release from the hydrogel device with in first 30 min, while the 90% of thallium-201 was released from the device within the next 45 min. Poly(HEMA) hydrogel devices synthesized using 2%–10% of EGDMA showed approximately 25% of thallium-201 release within the first 30 min, while only 45% of thallium-201 release was observed within the next 105 min; thallium-201 release took >6 h, confirming the sustained release property of poly(HEMA) hydrogel device. Conclusion: Poly(HEMA) hydrogel device synthesized using 10% of EGDMA as a cross-linker showed maximum sustained release behavior. Polymeric hydrogel synthesized using 1% of EGDMA as cross-linker showed poor mechanical property, while hydrogel device with 10% of EGDMA was brittle in nature. Polymeric hydrogel with 2% of EGDMA showed the optimal property with sustained release behavior.
[TAG:2]PV57: Comparison of 188Re/4-hexadecyl 1, 2, 9, 9–tetramethyl 1, 4, 7–diaza-1,10-decanethiol lipiodol retention in liver labeled with two different methods (centrifugation and shaking method) in hepatocellular carcinoma[/TAG:2]
Priyanka Singh, Priyanka Gupta, Shreya Dutta Gupta, Shamim Ahmad Shamim, Chndrasekhar Bal
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Background and Objectives: To compare 188Re/4-hexadecyl 1, 2, 9, 9–tetramethyl 1, 4, 7–diaza-1,10-decanethiol (HDD) lipiodol retention in liver labeled with two different methods (centrifugation and shaking method) in hepatocellular carcinoma. Materials and Methods: 188Re HDD-conjugated lipiodol was prepared using lyophilized HDD kit and lipiodol. Sodium perrhenate eluate was added to HDD kit and mixed. pH was adjusted by phosphate buffer. 188Re/HDD complex was boiled at 100°C for 1 h followed by cooling. 5–6 ml of lipiodol was added and vigorously shaken for 10 min followed by centrifugation at 3000 rpm for 15 min. Final product 188Re-labeled lipiodol was extracted. In another method, vial was vigorously shaken for 30 min to form 188Re-HDD/lipiodol in solution form. The whole solution used for transarterial infusion. Scout dose (5 mCi) was injected to determine pulmonary shunt and dosimetry purpose followed by therapeutic dose (30–80 mCi). Patients were kept under observation up to 72 h. Whole-body image acquisition was done for scout and at 17, 24, and 48 h after administration of 188Re-HDD-lipiodol. Regions of interest were drawn around the total body, liver (including tumor), lungs, bladder, and background region which was background corrected to determine source organ residence times and tumor retention. Results: Radiolabeling yield of 188Re-HDD-lipiodol by centrifugation method was 40%–50%, while it was 100% by shaking method. By centrifugation method, normal radiotracer biodistribution was observed in liver, minimal uptake in lungs, whereas free rhenium perrhenate uptake was observed in the thyroid gland and stomach with a high noticeable uptake in lungs when labeled by the conventional shaking method. No radiotracer concentration was observed in any organs except liver in patients injected by centrifugation method compared to uptake in salivary glands, lungs, and stomach activity noted in patients injected by shaking method. Percent retention of 188Re-HDD-lipiodol in the liver including tumor was observed to be persistently high at all time points by centrifugation method compared to shaking method. Percentage retention at 0, 17, 24, and 48 time points are 9.7, 9.8, 11.7, 14.5 and 2.40, 4.77, 5.74, and 5.72 by centrifugation and shaking method, respectively. Conclusion: The higher retention percentage in the liver with remarkably high liver/tumor to background ratios and confinement of the radioconjugate to the tumor favor centrifugation method over conventional shaking method.
| PV58: A new ligand for assessment of translocator protein (18 kDa) | | |
Vinay K. Singh, Anjani K. Tiwari
Department of Chemistry, DSMN University, 1Department of Chemistry, BBAU Central University, Lucknow, Uttar Pradesh, India
Background and Objectives: Radioligand development for translocator protein (18 kDa, TSPO) to studying its role in the activation of glial cells in the injured brain as well as in neurodegenerative diseases is one of the most critical issues of imaging sciences. Most of radioligands bind TSPO with high affinity in small animals; however, their specific binding is reduced in the human brain. Moreover, some such as PBR28 exhibited mixed affinity with TSPO in “binder” and “nonbinder” human subjects. Hence, new candidate for TSPO ligand with different structural skeleton should be desirable from this point of view. Here, we have synthesized a new series of ligands 2-[5-(4-alkoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenyl acetamide and evaluated in vitro and in vivo for TSPO expression in the brain. Materials and Methods: The specific ligand and their precursors were synthesized by easily reproducible methods. To determine specific binding with TSPO on neuroinflammation of the brain, radioefficacy studies were performed in ischemia rat model. Finally, their efficacy was also evaluated for binder and nonbinder brain through human to see the effect of TSPO polymorphism rs6971. Results: Biodistribution studies confirm high accumulation of radioactivity in the TSPO-rich organs such as lungs, heart, kidney, and adrenal glands. Blocking experiments with unlabeled TSPO-specific ligands MPMB or (PK11195) minimized the difference in uptake between the two sides. Computational and preliminary studies showed that the binding of this compound may not be significantly affected by the TSPO polymorphism rs6971. Conclusion: On the basis of above-said data, these acetamidobenzoxazolone ligands have shown promising aspect to image TSPO. In vitro autoradiography on coronal brain sections obtained from Alzheimer's disease patients confirms its high affinity for TSPO in both binder and nonbinder brains. Further primate's study is required to evaluate the usefulness of this compound before clinical use.
| PV59: Radiolabeling and in vitro evaluation of 68Ga-macroaggregated albumin formulated using BRIT TCK-56 kits | | |
Ashok R. Chandak1,2, Sutapa Rakshit2, Archana Ghodke1, R. Vanaja1, H. H. Shimpi2, Sharmila Banerjee1,2
1BRIT, Vashi Complex, Navi Mumbai, 2RMC, BARC, TMH Annex, Parel, Mumbai, Maharashtra, India
Background and Objectives: The long shelf-life of 68Ge/68Ga generator is simple to use and a steady source of the positron emission tomography (PET) radionuclide for nuclear medicine centers without cyclotron. Labeling of macroaggregated albumin (MAA) particles with 68Ga is a better alternative to 99mTc. In this respect, the commercial TCK-56 kits supplied by BRIT were labeled with 68Ga for lung perfusion imaging. The present work deals with the radiolabeling and in vitro evaluation of BRIT TCK-56 kits (MAA) with 68Ga3+ eluted from a commercial 68Ge/68Ga generator for lung perfusion imaging. Materials and Methods: BRIT commercial MAA cold kits were used for labeling with 68Ga by direct and modified method. In modified method, stannous and other dissolved contents of the cold kit were separated and washed MAA particles were labeled with 68Ga, and in direct method, cold kit content was disperse in 0.5 M acetate buffer and used for labeling. The synthesis was carried out aseptically in Eckert and Ziegler automated module. Physicochemical QC, ST/BET, and particle size distribution were performed for labeled MAA particles. To check free 68Ga content, small amount of 68Ga-MAA product was passed through 0.22 μm membrane filter and evaluated. The stability of labeled product was also evaluated up to 3 h. Results: The radiochemical purity (RCP) of 68Ga-MAA prepared with modified method was found to be >95% which was found 60% with direct labeling method. Particle size was found in the range of 10–60 μm and the pH was found to be 4–5.5. In filtration, <2% of free 68Ga activity was found in the filtrate and found to be quick and alternative method to confirm 68Ga-MAA RCP. Conclusion: The physicochemical and microscopic evaluation of 68Ga-MAA prepared with modified method found suitable for clinical studies. Furthermore, automated synthesis allows radiopharmaceutical production of in compliance with the GMP guidelines.
| PV60: Animal biodistribution and in vivo imaging study of 68Ga-macroaggregated albumin preparation using commercial macroaggregated albumin cold kit (TCK-56): An attractive alternative to 99mTc-macroaggregated albumin | | |
Ashok R. Chandak1,2, Sutapa Rakshit2, Sangita Lad2, Y. Pawar2, H. H. Shimpi2, Sharmila Banerjee1,2
1BRIT, Vashi Complex, Navi Mumbai, 2RMC, BARC, TMH Annex, Parel, Mumbai, Maharashtra, India
Background and Objectives: 99mTc-labeled macroaggregated albumin (MAA) has been recognized as a suitable imaging agent for lung perfusion studies and for planning of selective internal radiation treatment of metastatic liver cancer. Due to in vivo attenuation and scatter of γ photons, single photon emission computed tomography (SPECT) has limitations in resolution and sensitivity, which affect its accurate quantification. In comparison, the positron emission tomography (PET) tracer 68Ga-MAA is expected to provide an excellent alternative to 99mTc-MAA. The present work is an attempt to produce pharmaceutical grade 68Ga-MAA preparation and carry out its biodistribution in mice and PET-CT imaging in rabbit with the aim of using in human lung perfusion studies. Materials and Methods: 68Ga-MAA was prepared aseptically in Eckert and Ziegler automated module using 0.5 M acetate buffer. The preparation with suitable physicochemical and biological properties was used for animal biodistribution study. Around 200 μCi (0.1 ml) product was injected through lateral tail vein of Swiss mice and was sacrificed at each selected time points and the organs were collected and counted. Decay corrected percentage injected dose per gram of each organ was calculated. Around 500 μCi (0.2 ml) of labeled 68Ga-MAA particles were injected into rabbit through ear vein and PET-CT imaging were carried out after 30 min and 1.5 h postinjection. Results: The RCP was found to be more than 95% and BET;ST of the prepared product was found to be within specified limits. More than 90% of the injected activity was localized in mice lungs at 30 min, and there was no change found at 1 h p.i. The biodistribution data in mice are well correlated with PET/CT imaging of rabbit. These results indicate that the labeled 68Ga-MAA product was stable in biological system. Conclusion: In vivo biodistribution in Swiss mice and PET-CT imaging of the rabbit showed similar pattern with optimal uptake in lungs. Further clinical studies in human will be planned after ethical approval.
| PV61: Laminin-based peptidic (DO3A-YVARLI) single photon emission computed tomography imaging probe for angiogenesis | | |
Raunak Varshney, Meenakshi Saklani, Rashi Mathur, Ankur Kaul, Anil K. Mishra
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
Background and Objectives: Angiogenesis is essential in physiological such as wound healing and the menstrual cycle and pathophysiological processes, i.e., diabetic retinopathy, tumor growth, and metastasis. In tumor angiogenesis, vascular endothelial growth factor (VEGF)/VEGF receptor signaling pathway and cell adhesion molecule such as laminin and integrin αvβ3 play key roles in regulating the growth of new blood vessels. Laminins are cross-shaped trimeric glycoproteins and their cell–ECM basement membrane interactions are vital in angiogenesis. Laminin is of specific interest in angiogenesis as it mediates endothelial cell adhesion, differentiation, and tube formation. Furthermore, laminin transmemberane receptor is overexpressed in various cancers such as gastric, breast, cervical, colon, colorectal, lung, ovarian, pancreatic, and prostate. The rationale of this study was to develop modified DO3A-YVARLI as indicative of angiogenesis by facile solid phase synthesis. Materials and Methods: The peptide was synthesized on solid phase by Fmoc-chemistry on Rink amide resin. The Fmoc group on N-terminal of tyrosine amino acid was deprotected using 20% (v/v) solution of piperidine in DMF. The NH2 group on resin was alkylated with the help of chloro-acetylchloride in NMP/DIPEA and conjugated to DO3A in the presence of K2CO3. On completion, the peptide conjugate (DO3A-Tyr-Val-Ala-Arg-Lys-Ile) was cleaved from resin using TFA cocktail with scavenger. The conjugate was radiolabeled with 99mTc in aqueous solution at pH 6.5–7.5. Results and Conclusion: The synthetic yield of DO3A-IKVAV was ~65% yield. Peptide was purified by HPLC (12.49 min) and characterized by molecular mass of 734.02 [M + H] +peak in mass spectroscopy. In hemolytic studies, maximum percentage of erythrocytes lysis was observed to be 4.63.The conjugate binds with 99mTc with high specific activity and efficiency (98.4%). The stability in serum indicated that 99mTc remained bound to the drug up to 24 h. The in vivo biodistribution and blood kinetic studies exhibited rapid clearance of the radiolabeled complex and excretion through the hepatobilliary and renal route. Further biological evaluation for angiogenic effect is under progress to prove it significant stronghold as an excellent single photon emission computed tomography imaging probe.
| PV62: Evaluation of radiolabeled EDTA-bis-cysteamine-conjugated gold nanoparticles as theranostic agent | | |
Rashi Mathur, Raunak, Ankur Kaul, Ragini Singh, A. K. Mishra
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Timarpur, Delhi, India
Background and Objectives: Nanomaterials and their unique nanoscale properties are revolutionizing the area of tumor targeting for both diagnostics and therapy (theranostics). Noble metal nanoparticles, especially that of gold, have been evaluated for delivery, diagnosis, and treatment. Despite its extraordinary inertness under most conditions, Au is well known for its ability to form a relatively strong (about 184 kJ/mol) gold−thiolate (Au−S) bond with compounds containing the thiol (−SH) or disulfide group (S−S). By varying the functional group at the distal end of a thiol or disulfide molecule, well-defined interfaces can be developed that are specifically designed to interact or remain inert within a biological system. The present work was undertaken to synthesize gold nanoparticles (AuNPs) conjugated EDTA-bis-cysteamine with the intent of forming a stable chelate such as nanosystem which can be used as a multimodality imaging platform while retaining its therapeutic potential. Materials and Methods: The study was conducted in two steps, first the synthesis of AuNP was done by the established Turkewich method and was then conjugated the synthesized targeting ligand EDTA-bis-cysteamine. Successful synthesis of EDTA-cysteamine was confirmed by mass spectroscopy and NMR. These synthesized native AuNPs were characterized by UV spectroscopy, TEM, SEM, and DLS. The EDTA-bis-cysteamine-AuNP conjugate was characterized by UV spectroscopy, TEM, and DLS. The EDTA-bis-cysteamine AuNPs was evaluated for its pharmacokinetics, biodistribution, and tumor regression abilities after radiolabeling it with 99mTc. Results and Conclusion: Native AuNP showed particle size distribution with 90.3% of particle to be 48.56 nm and a PDI of 0.469. The size was also characterized by TEM and SEM and a strong absorption at 525 nm in UV-Vis. Conjugation with EDTA-bis cysteamine shows a red shift and appearance of a new attributed to the conjugation. The pharmacokinetics, biodistribution, and single photon emission computed tomography imaging of 99mTc-EDTA-AuNPs show an expected distribution and an initial fast clearance. Tumor regression studies performed show that at the dose given, the tumor shows substantial regression, indicating the accumulation of the nanoconjugate due to EPR effect. This accumulation of gold nanoconjugate at the tumor site will eventually lead to selective heating of target cells upon laser irradiation, minimizing potential damage to the healthy tissue during a nanobased PTT treatment.
| PV63: Rhenium-188: From generator to radiopharmaceutical preparation | | |
Anupriya Chhabra, Yogesh Rathore, Priya Bhusari, Rakhee Vatsa, Bhagwant Rai Mittal, Jaya Shukla
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Background and objectives: Rhenium-188 (Re-188) is a theranostic radioisotope used widely for therapies such as keloid treatment, bone pain palliation, and HCC. It has βmax energy = 2.12 MeV, tissue penetration = 11 mm and is easily available as it is generator produced and cost effective. As the generator gets old, activity versus volume ratio gets decreased; hence, concentrating Re-188 will result in greater yields in the preparation of various Re-188 radiopharmaceuticals. Materials and Methods: IC-Ag resin was soaked for 30 h in silver nitrate solution and was loaded in syringe/readymade glass column. After conditioning the column with 5 ml HPLC grade water, 15 ml Re-188 eluted from W-188/Re-188 generator in normal saline was passed through the resin at a flow rate of 1–2 ml/min. The solution was further passed through QMA in which perrhenate was trapped and eluted with 1 ml normal saline. Various physicochemical and biological quality control tests were performed. For RCP, saline and acetone were used as mobile phase; for sterility testing, concentrated Re-188 was inoculated in tryptic soya broth and incubated in CO2 incubator at 37°C; for endotoxin estimation, PTS was performed. Concentrated Re-188 was used in the preparation of various radiopharmaceuticals such as Re-188-HEDP (1–2 ml), Re-188-lipiodol (2 ml), and Re-188-colloid (3 ml) and radiochemical yield was calculated. Results: 15 ml of 55 mCi Re-188 was concentrated to 1 ml volume having 54.5 mCi activity. The obtained solution was colorless, and Rf was 1 with both saline and acetone. No turbidity was observed in broth up to 7 days of incubation. Endotoxin levels were less than 0.25 EU/maximum volume of injection. Radiolabeling yield was >95% in all radiopharmaceutical preparation. Conclusion: System provide high specific Re-188 radioactivity in about 1/15th volume. Concentrated Re-188 can be used in the preparation of high yielding radiopharmaceuticals.
| PV64: Production of therapeutic doses of 131I-labeled lipiodol injection for the treatment of hepatocellular carcinoma | | |
Archana Mukherjee1,2, Rajwardhan Ambade1,2, Barkha Karkhanis3, Ashutosh Dash1,2, Aruna Korde1, 2, 3
1Division of Radiopharmaceuticals, Bhabha Atomic Research Centre, 2Homi Bhabha National Institute, Anushaktinagar, Mumbai, 3Radiopharmaceutical QCP, Board of Radiation and Isotope Technology, Navi Mumbai, Maharashtra, India
Background and Objectives: Transarterial radioembolization using 90Y-bearing glass spheres (Therasphere®) and polymeric selective internal radiation spheres (SIR-spheres®) is performed worldwide for therapy of hepatocellular carcinoma (HCC). Exorbitant cost of these agents is a major limitation for their use in developing countries like India. 188Re-HDD-lipiodol is envisaged as an alternative for therapy but availability of 188W/188Re generator restricts it wider use. 131I-labeled lipiodol can be easily prepared and supplied owing to suitable half-life of 131I, allowing convenient logistics of production and quality control checks before patient administration. The aim of this work was to perform regular production and supply of 131I-labeled Lipiodol injection as a cost-effective radionuclide therapy agent for the treatment of HCC. Materials and Methods: The patient dose preparation of 131I-labeled lipiodol requires high amounts of initial activity of 131I. The high energy gamma radiations (637KeV, ~7% abundance and Eβmax: 610 KeV) of 131I pose considerable safety-related limitations for radiolabeling. Semi-automated modular system was designed and fabricated to ensure operator safety as well as pharmaceutical purity and safety of the product. Regular production of 131I-labeled lipiodol injection was carried out utilizing semi-automated synthesis module. In-process checks and physicochemical and biological quality control were carried out for the finished product. Radiochemical purity (RCP) of the product was estimated by paper chromatography using two solvents. Bacterial endotoxin test and sterility tests were carried out as per the pharmacopoeia standards. Therapeutic doses were supplied to nuclear medicine center for clinical evaluation. Results: Ten batches of 131I-labeled lipiodol injection were successfully produced with consistent radiochemical yield and RCP. All batches complied with specified quality criteria of RCP >99%, radioassay 0.66 GBq–1.072 GBq/mL (25–40 mCi/mL), BET <750 EU/VmL, and sterility as per the Indian pharmacopoeia standards. Decay corrected quantities of therapeutic doses of 131I-labeled lipiodol injection were supplied to nuclear medicine center for clinical studies in liver cancer patients. Single photon emission computed tomography images at 24 and 72 h p.i revealed desired retention of 131I activity in the liver. Conclusion: 131I-labeled lipiodol injection is available as a cost-effective alternative for the treatment of HCC through BARC/BRIT.
| PV65: Gallium-68 generator system: Left or right, which path to choose | | |
Saumya Shrivastav, Manish Dixit, Subhash C. Kheruka, Sanjay Gambhir
Department of Nuclear Medicine, SGPGIMS, Lucknow
Background and Objectives: Gallium-68 (68Ga) is of growing interest for the production of Ga-radiolabeled compounds used as tracer molecules in positron emission tomography (PET) imaging technique. To obtain 68Ga, the most common technique is the use of a 68Ge/68Ga generator. With a physical half-life of 68 min, availability independent of a cyclotron and excellent binding characteristics to chelators such as DOTA 68Ga have excellent properties for routine clinical application. The most widely implemented application of 68Ga at present is the imaging of somatostatin receptor-positive tumors. This application, most specifically in the imaging of neuroendocrine tumors (NETs), has taken of the development of different tracers for clinical imaging. The commercially available generators are the only source of Ga-68 for labeling. There are only few commercially manufacturers such as ITG, E&Z, Germany, and ithemba. All available generators have different solid phase packing materials and eluting solvents with varying pH and concentrations. With this, different manufacturers claimed to have their own developed synthesis modules for better and efficient labeling of few of selected clinical biomolecules. Keeping all this in mind user is get confused which generator along with module or generator alone will work or need to buy all together with restricted labeling protocols. Selection of generator and/or synthesis module becomes a nightmare for the end-user, especially for clinical applications. Methods: This paper reviews and discusses the chemistry of the available generators and how the chemistry of labeling was performed with different pH and eluted Ga-68 concentration to perform efficient and quality labeling protocols. In short, we review the international literatures to find the answer to our most important questions and query them why generators are specific with parent's company synthesis modules. Results and Conclusion: While reviewing various scientific published works, we concluded that understanding the chemistry of Ga-68 elute and understanding the labeling chemistry, we will use any Ga-68 generator with any automated and/or manual synthesizer with varieties of clinical usable biomolecules.
| PV66: 177Lu-DOTA-NHS-trastuzumab: Radiolabeling, quality control, and in vitro stability | | |
Geetanjali Arora, NishikantAvinash Damle, Chandrasekhar Bal, Madhavi Tripathi, Ahitagni Biswas1, Ritesh Kumar1, Piyush Mishra2, Anurag Srivastava2, Chitresh Sharma3, Pramod K. Julka1
Department of Nuclear Medicine, 1Radiotherapy, 2Surgery and 3Surgical Oncology, AIIMS, New Delhi, India
Background and Objectives: Breast cancer patients are usually tested for the level of HER2 in their tumors to assess feasibility of trastuzumab therapy. Physical characteristics of 177Lu make it suitable for radioimmunotherapy (RIT). We present here the preliminary results of standardization of trastuzumab radiolabeling with 177Lu, quality control, and in vitro stability conducted at our institute. Materials and Methods: The conjugate of DOTA-NHS and trastuzumab was prepared by incubating the antibody with 20-fold molar excess of DOTA-NHS in 10 ml of ammonium acetate buffer. 10 ml of the prepared ammonium acetate buffer was taken in a sterile glass vial. 116 ul of trastuzumab stock solution (260 mg/ml, 148,400 g/mol; CANMab; Biocon) was added to it followed by the addition of 70 ul of DOTA-NHS stock solution (4 mg/ml, 688 g/mol; macrocyclics). The vial was then incubated at 37°C for 3 h followed by 21 h incubation at room temperature. The solution was stirred at regular intervals. Trastuzumab complex was purified using PD10 column and ammonium acetate buffer. 3 mCi of 177LuCl3 was added to 0.5 ml of the purified fraction of antibody conjugate and incubated at 37° for 3 h. The sample was stirred at regular intervals. Labeling efficiency (LE) was checked using instant thin layer chromatography (ITLC). In vitro stability of the labeled compound was checked using ITLC at 6 and 21 days at room temperature (25°C). Factors affecting LE were studied. Results: In total, nine synthesis were carried out. LE was >95% (Rf = 0) in six synthesis with specific activity >15 mCi/ug of 177Lu and 37°C incubation temperature. To study the effect of specific activity, two syntheses were performed at specific activity of 11.4 and 4 mCi/ug. The LE for these syntheses was 64% and 52%, respectively. In one synthesis, the incubation temperature was 25°C and the LE achieved was 80%. In one of the six samples with LE >95%, stored at 4°C, the radiochemical purity of the product was rechecked at day 6 and 21.The radiochemical purity was found to be 89% and <50%, respectively. Conclusion: The study was conducted as a prelude to the patient studies for standardization of the labeling technique at our laboratory and test the variants such as specific activity, incubation temperature, and stability. With the limited number of synthesis that could be performed, we found that consistently high LE is achieved at specific activity >15 mCi/ug of 177Lu and 37°C incubation temperature. Furthermore, radiochemical purity of the labeled compound falls below 90% in one half-life of 177Lu.
| Others Track | | |
| OP54: Ordered subset expectation maximization parameters for image reconstruction in Tc99m-MIBI myocardial perfusion single photon emission computed tomography in Indian population | | |
Pankaj Dheer, Priyanka Gupta, Sameer taywade, Averileciah Passah, Anil Kumar Pandey, Chetan Patel
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: To establish the most appropriate ordered subset expectation maximization (OSEM) parameters for image reconstruction in Tc99m-MIBI myocardial perfusion single photon emission computed tomography (MPS), and comparison with filtered backprojection (FBP)-reconstructed images. Materials and Methods: Ninety-nine stress-rest MPS studies with 47 normal and 52 abnormal patients were retrospectively processed and analyzed. Each study was reconstructed using sixteen different combinations of iterations and subsets (2–2, 2–6, 2–10, 2–16, 4–2, 4–6, 4–10, 4–16, 6–2, 6–6, 6–10, 6–16, 8–2, 8–6, 8–10, and 8–16). Images were reconstructed both with and without postreconstruction Butterworth filter (cutoff frequency and order of 0.4 and 10 for stress and 0.52 and 5 for rest images, respectively) for each combination of iteration subset (32 images for each patient). A total of 3168 images were evaluated. These images were graded by two blinded nuclear medicine physicians on a scoring scale of 1–4 (4 = best-image quality). The iteration subset combination was determined for the best images of each patient both with and without postreconstruction Butterworth filter. The best-quality image was compared with FBP-reconstructed image using standard vendor provided parameters. The interobserver agreement between both physicians was obtained using kappa statistics. Results: The best images in terms of image quality were obtained using a combination of 4 iteration 6 subsets for both with and without postreconstruction Butterworth filter. The value of kappa for interobserver agreement between both the physicians for images reconstructed using OSEM with Butterworth filter was 0.570 (moderate agreement) and for OSEM without Butterworth filter was 0.857 (almost perfect agreement). On comparison, FBP images were better than OSEM-reconstructed images without postreconstruction Butterworth filter (P < 0.0001 calculated using Fischer's exact test) with substantial agreement (kappa = 0.628) between the two observers. However, OSEM-reconstructed images with postreconstruction Butterworth filter were better than FBP-reconstructed images and a moderate agreement (kappa = 0.486) was obtained between two observers. Conclusion: The most appropriate OSEM reconstruction parameter for image reconstruction in Tc99m-MIBI MPS in Indian population is 4 iteration 6 subset combination, for both with and without postreconstruction Butterworth filter. Images reconstructed with FBP were better than the images reconstructed with OSEM using 4 iteration 6 subset combination without postreconstruction Butterworth filter. However, image reconstruction with OSEM using 4 iteration 6 subset combinations with postreconstruction Butterworth filter yielded the best images.
| OP55: Biodistribution and dosimetry of indigenous 131I-rituximab in B-cell lymphoma: Pilot study estimating patient-specific dose comparing the two dosimetric methods | | |
Aadil Adnan
Radiation Medicine Center, BARC, Mumbai, Maharashtra, India
Background and Objectives: To examine the biodistribution and dosimetry of indigenously developed and radiolabeled 131I-rituximab, using the chimeric monoclonal antibody, in patients of B-cell lymphoma for its potential use. Materials and Methods: This was a prospective study involving patients of B-cell non-Hodgkin's lymphoma NHL who underwent low-dose diagnostic scan for the dosimetric and biodistribution studies. The study was presented and approved by the Institutional Scientific and Medical Ethics Committee, and the product was approved by the regulatory body of DAE, the Radiopharmaceutical Committee, for preliminary dosimetric studies. Patients with documented CD20-positive NHL who were planned for and received rituximab-based chemotherapy under medical oncology supervision were recruited. Soon after the intravenous (IV) rituximab infusion (4–6 h), the diagnostic dose of indigenously produced 131I-rituximab was administered by IV infusion. Serial planar (anterior and posterior) whole-body gamma camera images were undertaken soon after the infusion (prevoid and postvoid) and thereafter on day 1, 2, 4, and 6. A high energy collimator was used. A standard source of 131I, with known activity, was imaged for whole-body count correction for physical decay of radioiodine and to obtain the percent injected activity remaining at each time point. Results: Thirteen patients underwent assessment in this prospective study following the aforementioned protocol. The calculated patient-specific dose from the cumulative activity, which will give a whole-body radiation absorbed dose of 75 cGy, using the MIRD schema, ranged from 83.66 to 171.09 mCi (mean 107.73 ± 23.35 mCi and median 99.93 mCi). The mean residence time of this indigenous radiopharmaceutical was 69.54 h. Within first 48 h, ≥50% of the injected activity was cleared, and by 144 h, ≥80% of the injected activity was cleared from the body in all patients. The patient-specific dose that would give a whole-body radiation absorbed dose of 75 cGy, calculated by mean residence time and activity-hours, ranged from 71.75 mCi to 167.85 mCi (mean 96.66 ± 25.07 mCi and median 92.46 mCi). With respect to organ-specific dosimetry, apart from blood pool (3.77 Gy) and spleen (4.02 Gy), the organs with decreasing order of mean radiation absorbed dose were lung (0.97 Gy), liver (0.69 Gy), and kidneys (0.7 Gy) calculated for proposed therapeutic doses of the product. Conclusion: The indigenous product demonstrated kinetics similar in lines with that of approved commercially available radiopharmaceuticals: in none of the organs, there was dose-limiting radiation exposure (≥20 Gy) at the proposed therapeutic doses of this indigenous 131I-labeled rituximab product.
| PP61: Comparison of Q.Clear and VUE pont HD reconstruction positron emission tomography reconstruction algorithms in nodal staging of early operable breast cancers | | |
G. Chandran, S. Pooja, J. Sangeetha, S. John, C. Piyush, N. Satish
Department of Nuclear Medicine, MIOT international, Chennai, Tamil Nadu, India
Background and Objectives: Q.Clear reconstruction algorithm, a penalized likelihood iterative reconstruction, improves the signal-to-noise ratio compared to conventional VUE pont HD reconstruction (VPHD) algorithms on GE positron emission tomography-computed tomography (PET/CT) systems. We compared the two algorithms in image quality and various quantification parameters in nodal staging of early operable breast cancers. Materials and Methods: Retrospective analysis of 21 oncology whole-body 18F-labeled fluoro-2-deoxyglucose (18F-FDG) PET/CT scans in patients with early breast cancers (mean primary tumor size – 3.3 cm) acquired on GE-IQ 5 ring PET/CT scanner and reconstructed using VPHD (filter cutoff-5.5 mm, 12 subsets, and 4 iterations) and Q.Clear algorithm (using B values of 350). Time of acquisition was 1.2 min/bed position. Both the reconstructed images were assessed independently by two experienced readers, and various parameters such as contrast-to-noise ratio (CNR), SUVmax, and SUVmean were calculated for regional nodes using VPHD (V) and Q.Clear (Q) reconstruction algorithms. Results: Of the 21 patients, 42% (n = 9) patients had axillary nodes, 19% (n = 4) had ipsilateral supraclavicular nodes, and 28% (n = 6) has ipsilateral nodes visualized on PET/CT images. Mean SUVmax (V) and mean SUVmax (Q) of the primary tumors were 8.3 and 8.8, respectively (+6% change). Mean SUVmax (V) and mean SUVmax (Q) of the axillary nodes were 6.8 and 8.04, respectively (+16% change). Mean SUVmax (V) and mean SUVmax (Q) of the ipsilateral supraclavicular nodes were 5.42 and 6.2, respectively (+13% change). Mean SUVmax (V) and mean SUVmax (Q) of the ipsilateral internal mammary nodes were 1.9 and 2.75, respectively (+31% change). CNR (V) and CNR (Q) for the internal mammary nodes were 9.4 and 15.08, respectively (+38% change) and for the axillary nodes were 37.5 and 37, respectively. Conclusion: Q.Clear reconstruction algorithm potentially can further improve the accuracy of PET/CT in nodal staging of early operable breast cancers as it generates a significantly higher CNR and SUVmax values compared to conventional VPHD algorithm. Q.Clear could be especially useful in increasing the reader's confidence in identification of subcentimeter-sized faintly FDG avid internal mammary nodes.
| PP62: Effect of differences in tumor region of interest delineation on radiomic features: comparison of semiautomated tumor segmentation methods | | |
Ashish Kumar Jha, Sneha Mithun, B. S. Umesh Kumar, Vinay R. Jaiswar, R. V. Prasad1, V. angarajan, Andre Dekker2, Leonard Wee2
Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, 1Philips Innovation Campus, Philips India, Bengaluru, Karantaka, 2Department of Radiation Oncology (MAASTRO Clinic), Maastricht, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands
Background and Objectives: Accurate and consistent delineation of tumor volume is a challenging task for radiologists as well as for radiation oncologist. Semiautomated segmentation techniques are now available in commercial clinical imaging workstations for tumor region-of-interest (ROI) generation. Radiomics refers to computerized extraction of quantitative tumor features directly from radiological images and is thus dependent on reproducible tumor ROI delineations. We compare two of the most commonly used semiautomated segmentation techniques based on a Dice spatial similarity metric and concordance of radiomics features between two independent segmentations of the same tumor. Materials and Methods: Pretreatment hybrid positron emission tomography/computed tomography examinations on 30 nonsmall cell lung carcinoma patients were used in this ethics-approved retrospective study, and ROIs of the primary lung tumor were generated using SUV threshold-based segmentation on a GE Advantage Workstation and region-growing segmentation on a Philips Intellispace Discovery workstation. A Dice similarity coefficient (DSC) was used to quantify the consistency of segmentation between the two methods. 112 radiomic features per patient were extracted from each ROI and reproducibility was assessed using the concordance correlation coefficient (CCC) per feature. We also considered the sensitivity of DSC on tumor volume and SUVmax. Results: The median DSC over all 30 subjects was 0.722 (range: 0.443–0.902), demonstrating a high degree of interpatient variability when applying the two segmentation techniques. An overall median CCC of 0.741 (range: 0.074–0.982) suggests reasonable robustness with respect to segmentation, but the distribution is skewed by some features having poor reproducibility. Out of 112 radiomic features, 38 features, 60 features, and 79 features had CCC value >0.8, >0.7, and >0.6, respectively. The differences between ROIs appeared to be independent of tumor volume or maximum uptake. No immediately obvious pattern was observed among those features that were poorly reproducible with respected to ROI differences. Semiautomated ROI delineation by either SUV threshold or region-growing was tested on two independent imaging workstations. There is a high degree of inter-subject variability between the two segmentation methods requiring deeper investigation. The impact on radiomic features can be quite significant, leading to loss of reproducibility of 25%–40% of the tested features due to inconsistent tumor ROIs. While semiautomated segmentation may significantly reduce manual workload, our findings suggest that both methods still need to be validated against human-expert consensus delineations. Conclusion: Details of the tumor delineation method in radiomic studies should be carefully documented, and reproducibility of potentially predictive features should be checked before being used in predictive/prognostic model development.
| PP63: Deferoxamine attenuates the neurotoxic effect of 6-hydroxy dopamine in SH-SY5Y cell line by inhibiting apoptosis and modulating autophagy | | |
Jyotirmoy Rakshit, Jaya Bandyopadhyay, Karthik Kumar Gowrishetty
Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, West Bengal, India
Background and Objectives: Involvement of iron and its role in generation of cellular reactive oxygen species (ROS) through Fenton and Haber–Weiss reaction is a very common phenomenon behind neurodegeneration. In this context, iron chelation therapy is a very promising approach to prevent or inhibit the progression of different neurodegenerative disorders. However, till date, it is unclear that which molecular pathway is involved in this neuroprotective activity.[1] Hence, the major objectives are to determine the efficacy of the intracellular iron chelation against neuronal cell death mediated by one of the neurotoxic agent 6-hydroxy dopamine (6-OHDA) and identify the molecular mechanism behind the iron chelation-mediated neuroprotection. Materials and Methods: Human neuroblasomal cell line SH-SY5Y was used as a cellular model for this study. Cytotoxic effect of 6-OHDA and its amileoration by DFO was assessed by MTT assay and LDH assay. Hochest staining and acridine orange (AO) staining were used to determine the nuclear morphology and intercellular autophagic flux, respectively. Intracellular ROS generation was quantified by di-chloro flurocine diacetate assay. Expressional level of apoptotic genes (cleaved CASPASE-3 and cleaved PARP) and autophagy-related genes (LC3B and SQTM/p62) were analyzed by Western blotting. Results and Conclusion: In cytotoxicity assay, it was observed 150 μM of 6-OHDA is its IC50 and 100 μM of DFO was the optimum dose to study its ameliorating activity. Spectroflurometric analysis showed that with DFO pretreatment, intracellular ROS generation by 6-OHDA was reduced. The nuclear morphology was disrupted, i.e., condensed and fragmented nucleus was observed in 6-OHDA-treated cells which were further restored by DFO pretreatment. Simultaneously, the expression of apoptotic genes (cleaved CASPASE-3 and cleaved PARP) was also reduced due to the DFO pretreatment followed by 6-OHDA treatment, as compared to the only 6-OHDA-treated cells. Thereafter, the modulation of autophagic activity was monitored to check whether this pathway has any correlation with the above-mentioned phenomenon. Thus, in this study, it was clearly observed the metachromatic shift of AO from green to red, due to the increased acidification in 6-OHDA-treated cells which was reduced in DFO-pretreated cells. In immunoblotting analysis, increased expression or deposition of LC3B due to 6-OHDA treatment clearly depicted the change in autophagic flux[3] which was further normalized by DFO pretreatment. As per conclusion, this study confers the antiapoptotic and autophagic activity of DFO against neuronal injury.
| PP64: Optimization of number of principal components to be used for reconstructing 99mTc-MDP bone scan for reporting purpose | | |
Anil Kumar Pandey, Sunder Lal, Akshima Sharma, Rakesh Kumar, Chetan Patel, Chandra Sekhar Bal
Department of Nuclear Medicine, AIIMS, New Delhi, India
Background and Objectives: Principal component analysis (principle components [PCs]) is a multivariate technique and can be used for transforming the observed variables into a set of new variables, the PCs, which are uncorrelated and explain the variation in the data. Thus, it allows reducing “image” data set to a lower dimension to reveal the structures or the dominant types of variations in image. The objective of this study was to find the optimum number of PCs, which can be used to reconstruct the image for the purpose of reporting 99mTc-MDP bone scan. Materials and Methods: 224 99mTC-MDP bone scan images were included in this study. The zero padding around the DICOM images was removed; the intensity values were scaled in the range (0, 255) and saved in PNG format for PCs analysis. The methodology for image processing consisted five steps: (1) perform PCs analysis of the image, (2) reconstruct the image with the assigned number of PCs, (3) calculate the mutual information (MI) between the input and reconstructed image, (4) if calculated MI is less than the assigned MI value, repeat the procedure by incrementing the number of PCs by one else exit from the loop, and (5) save the last reconstructed image. The assigned MI values were equal to 0.70, 0.80, and 0.90 and the initial assigned numbers of PCs were 3, 20, and 30. A set of 1084 output images were reviewed by NMPs and they labeled each images either 0 for not acceptable and 1 for acceptable image. The image processing and the data analysis were performed using R version 3.4.1. Results and Conclusion: Approximately 75% (162 out of 215) images reconstructed with retaining 20 PCs were acceptable. Approximately 82% (176 out of 215) images reconstructed with retaining 30 PCs were acceptable. In case of nine images, the MI equal to 0.70 could not be achieved even with the images reconstructed with retaining 256 PCs. The optimum number of PCs that can be used to reconstruct the image for the purpose of reporting 99mTc-MDP bone scan is equal to 30.
| PP65: Repeated irradiation of fluorine-18 enhances biological and biochemical changes in cells: an in vitro prospect study | | |
Tanmoy Mondal, Amit Nautiyal1, Aruna Kaushik2, Deepanjan Mitra1, Alpana Goel3, Subrata Kumar Dey
Department of Biotechnology, MaulanaAbulKalam Azad University of Technology, Salt Lake, Kolkata, West Bengal, 1Institute of Nuclear Medicine and Molecular Imaging, AMRI Hsopitals, Dhakuria, 2Institute of Nuclear Medicine and Allied Sciences, S. K. MazumdarMarg, Timarpur, Delhi, 3Amity Institute of Nuclear Science and Technology, Amity University, Noida, Uttar Pradesh, India
Background and objectives: The increasing use of ionizing radiation in healthcare has raised concerns among the population. Positron emission tomography/computed tomography (PET/CT) is considered as a first-line imaging modality for the initial staging as well as follow-up of oncology patients. Effects of ionizing radiation are well known, but the effects of repeated exposure at diagnostic level dose are still unclear. In the present study, our aim is to find out the effect on cell after repeated low-dose exposure by 18F. Materials and Methods: V79 cell line was taken for the study and irradiated and cultured at 4 points of time till 48 h in an interval of 12 h using 18F isotope. The absorbed dose delivered at each point of time was 7.25 mGy. All samples were collected immediately after irradiation and processed for analysis. DNA double-strand breaks (DSBs) are generally accepted to be the most biologically significant lesion by which ionizing radiation causes cancer and hereditary disease. The comet assay and gamma H2AX foci formation assay were used to detect DNA DSBs. Cellular oxidative stress analyzed by estimating superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. Results: Tail moment significantly increased (35.83 ± 2.62) at 48 h sample, and the rate of increment is clearly observable after each time point of irradiation. Although the radiation induced comet formation is heterogenic in nature, the number of comet presenting cells increased by 87% ± 5% at 48 h. Like comet assay, the number of gamma H2AX foci formation also increased up to 57 ± 14.62. SOD activity at 12, 24, 36, and 48 h was 1 ± 0.06, 1.74 ± 0.02, 1.9 ± 0.07, and 2.18 ± 0.14. At 48 h, GPx activity also increased to 70.65% ± 12% from control sample. Conclusion: Nowadays, the frequency of radiological investigations is increasing rapidly for the diagnosis of disease, and it is very difficult to keep track of the patient's cumulative dose. Our finding clearly shows significant relationship between increments of biological and biochemical changes with repeated gamma exposure to the cell. However, it is known that radiation-induced DSBs are reversible. From this point of view, it may assume that all the damaged cells are getting repaired, but it is also a fact that lack of DSB repair at any point of time also increases the carcinogenic risk and genetic alterations. This in vitro study is helpful to understand the effects of repeated gamma exposure for a period of time in PET/CT procedure.
| PP66: Fractionated X-irradiation: A novel strategy to treat Alzheimer's disease-linked pathologies | | |
Anna Khan, Vijayta D. Chadha, Rozy Kamal, D. K. Dhawan
Centre for Nuclear Medicine, Panjab University, Chandigarh, India
Background and Objectives: The pathophysiology of Alzheimer's disease (AD) is closely linked to the formation of amyloid-β plaques and neurofibrillary tangles followed by marked atrophy in the brain. As the percentage of the population over the age of 65 years increases, the prevalence of the disease is anticipated to increase proportionately, making the treatment of AD a major health priority The conventional pharmacologic interventions target symptoms, but fall short of addressing underlying contributing factors for AD; thus, this study was designed to investigate the neuroprotective potential of low-dose fractionated X-irradiation in targeting β-amyloid deposits in Aβ-based animal model of AD. Materials and Methods: S.D. female rats received an intracerebroventricular injection of amyloid-β peptide (1–42) at stereotaxically defined points. Experimental sessions were conducted by segregating the animals into four groups: sham operated, β-amyloid injected (1 μg/μl), β-amyloid injection followed by cranial X-irradiation (10 Gy fractionated dose 2 Gy × 5 days), and only cranial X-irradiated group. Aβ plaques assessment was performed in histological sections. Neurobehavioral studies (elevated plus maze, Morris water maze, and active and passive avoidance tests) were undertaken to confirm memory impairment along with biochemical indices involved in the neurotransmission and antioxidant defense system. Results: Significant decrease in the amyloid deposits was observed in the post-irradiated group confirmed by histopathological sections of the cerebral cortex (H and E, Congo red, and Thioflavin T stains). These results were in concordance with the neurobehavioral tests that showed a significant improvement in Aβ-induced memory impairment in the animals subjected to the fractionated dose. Restoration of alterations in neurotransmission – cholinergic, dopaminergic, and serotonergic neurotransmitters – and the related enzymes (acetylcholine esterase, monoamine oxidase) further supported our results. Increase in expressions of neurodegenerative markers APP, GFAP, and Tau in amyloid-injected group and their decrease postirradiation also reveal the role of radiation in alleviating the neurotoxicity levels. Conclusion: Low-dose fractionated external beam ionizing radiation produces a significant reduction in amyloid-β deposits and Tau-expression, suggesting that fractionated radiation therapy can be used as novel treatment for AD-associated pathologies.
[TAG:2]PP67: Correlation of texture parameters with conventional semiquantitative parameter: standardized uptake values, metabolic tumor volume, and total lesion glycolysis in 18F-labeled fluoro-2-deoxyglucose positron emission tomography-computed tomography examination for lung carcinoma[/TAG:2]
Nivedita Rana, Bhagwant Rai Mittal, Kanhaiyalal Agrawal1, D. K. Dhawan2, A. K. Bhati3
Department of Nuclear Medicine, PGIMER, Department of 2Biophysics and 3Physics, Panjab University, Chandigarh, 1Department of Nuclear Medicine, AIIMS, Bhubaneswar, Odisha, India
Background and Objectives: In PET/CT imaging, standardized uptake values (SUVs), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) remain the conventional parameters for image analysis. However, texture analysis (TA) has emerged as a tool for image analysis in the recent past. Texture parameters (TPs) give us information from the image on the basis of interrelationships of pixels. In the present study, pattern of correlation of TPs with conventional parameters was studied in case of lung carcinoma patients. Materials and Methods: Thirty-three patients with lung carcinoma who underwent whole-body positron emission tomography/computed tomography were included in the study. Sixty-seven TPs other than conventional parameters (SUVmax, SUVmean, MTV, and TLG) were computed in these patients using MATLAB-based software CGITA-Chang-Gung Image Texture Analysis toolbox. This software computes various global, local, and regional TPs, based on different parent matrices. Conventional quantitative parameters, SUVmax; SUVmean2.5, MTV2.5, TLG2.5 (threshold of SUVmean = 2.5 g/ml); and SUVmean40, MTV40, TLG40 (threshold of 40% of SUVmax) were also calculated for primary tumor using another semi-automated software for VOI placement to validate the SUVs value obtained using CGITA software. Spearman rank correlation coefficient (r) of each TP with conventional parameters was computed. TPs were classified as strongly correlated for |r| ≥0.70, moderately correlated for 0.40 ≤ |r| < 0.70 and weakly correlated for |r| < 0.40 (level of significance P ≤ 0.05). Results: Only three first-order TPs were strongly correlated to SUVmax, SUVmean40, and SUVmean2.5. Number of TPs moderately correlated with SUVmax, SUVmean40, and SUVmean2.5 were 12, 3, and 11, respectively. Thirty-seven TPs were strongly correlated and 13 were moderately correlated with MTV2.5. Twenty-five were strongly correlated and 25 were moderately correlated with MTV40. Thirty-seven TPs were strongly and 11 were moderately correlated with TLG2.5. Twenty-seven TPs were strongly correlated and 21 TPs were moderately correlated with TLG40. Conclusion: Since most of the TPs were not strongly correlated with SUVs, it can be concluded that TPs are likely to give additional information than that provided by SUVs in case of lung carcinoma. However, in case of MTV and TLG, only few of the TPs are likely to give additional information than that provided by MTV and TLG.
| PP68: Guideline to dispose the decayed calibration sources to its country of origin/outside India | | |
Prathamesh Rajai, Natasha Singh, Amit Abhyankar
P. D. Hinduja Hospital and MRC, Mumbai, Maharashtra, India
Background and Objectives: Co-57, Cs-137, and Ge-68 are used in quality analysis. Ge-68 pin source/rod sources are utilized to calibrate positron emission tomography (PET) scanner systems. It is used as a transmission standard to provide a tissue density correction to permit accurate diagnostic scanning of patients. Ge-68 is uniformly dispersed in a ceramic medium with an outer stainless tube and permanently sealed end caps. However, since a long time, the disposal of these sources from India to its country of origin or within India has not been done. The objective of the study was disposal of decayed Ge-68 pin sources (procured in 2012, 2014) to its country of origin (U.S.A). Materials and Methods: Guideline for disposal is explained in ELORA by AERB. We first prepared the documents which were required by AERB after which they would provide us the export license for disposal. It took many attempts for us to get this export license. We had purchased this source from Eckert and Ziegler, USA. The suppliers provided all documents required related to disposal. We prepared all documents required regarding the transport as per the suppliers list of documents. After packing the pin sources, it was sent to Bangalore office G.E. along with all documents via special branch of Courier Company, and from there, it was sent to the USA for disposal. Results: Successfully disposed the decayed calibrated sources. Conclusion: In India, PET-computed tomography started approximately in 2003–2004, so many decayed Ge-68 pin sources and other calibration sources are lying in respective departments itself. Due to unavailability or clarity on procedure, no one really succeeded in disposal of these sources. However, now, with the help of ELORA guideline and supplier's guideline, we successfully sent our Ge-68 pin sources for disposal.
| PP69: In vitro dosimetry of phosphorus-32-incorporated radioactive patches for local radionuclide therapy | | |
Priyanka Gupta, Chandrasekhar Bal, S. P. Lochab, G. P. Bandopadhyaya, Rakesh Kumar
All India Institute of Medical Sciences, 1Inter University Accelerator Centre, New Delhi, India
Background and Objectives: Phosphorus-32 (P-32) can be used for local radionuclide therapy of various benign and malignant skin diseases. The aim of this study was to perform in vitro dosimetry of radioactive patches incorporating P-32 to determine the surface dose delivered, dose rate, depth in skin up to which significant radiation dose is delivered, and total radiation dose delivered up to that depth. Materials and Methods: Thermoluminescence dosimeter (TLD) 700H chip dosimeters were used for dosimetry of the in-house prepared circular radioactive patches of area 1 cm2 incorporating 1 mCi P-32 distributed uniformly over the patch. Dosimeters were first standardized which included calibration and selection of dosimeters with uniform response. The selected dosimeter chips were annealed and placed over the surface of the sealed patch for different time intervals, i.e., 1, 5, 10, 20, 30, 45, 50, and 60 min, to determine the dose delivered at the surface and to determine the dose rate. Thermoluminescence (TL) curves were obtained and absorbed dose corrected for weight was determined for each chip. Curves were plotted for time of exposure versus absorbed dose. For determining the depth in skin up to which significant radiation dose will be delivered, and to determine the total radiation dose delivered up to that depth, tissue equivalent material sheets (Lucite) of 1 mm were used. Measurements were done in duplicates using TLD 700H chips. TL curves were obtained for all the chips and graphs plotted for absorbed dose versus the lucite thickness. Percentage drop in dose rate and depth after which dose rate was negligible was determined. Dose delivered at different depths and cumulative dose delivered up to significant depth was found. Results: Dose delivered to the TLD chip at the surface of the patch at 1, 5, 10, 20, 30, 45, 50, and 60 min was found to be 0.1, 0.51, 1.02, 2.04, 3.07, 4..65, 5.14, and 6.16 Gy, respectively, and was found to have a linear relationship with respect to the duration of exposure. Dose rate at the surface was found to be approximately 6.16 Gy/h. The depth up to which significant radiation dose is delivered was found to be 3 mm after which it dropped to less than 1%. Total cumulative dose delivered up to 3 mm depth was found to be 8.3 Gy in 1 h. Conclusion: For a circular patch of 1 cm2 area containing 1 mCi of P-32 activity distributed uniformly, the surface dose rate was found to be 6.16 Gy/h. Total cumulative dose delivered up to 3 mm depth was 8.3 Gy/h.
| PV67: Optimization of the value of MEVIS Image Registration Toolkit module parameters for positron emission tomography/computed tomography image registration on personal computer | | |
Satnam Singh, Anil Kumar Pandey, Akshima Sharma, Chetan Patel, Chandasekhar Bal
Department of Nuclear Medicine, AIIMS, India
Background and Objectives: MEVIS Image Registration Toolkit (MERIT) is a framework for the implementation and usage of image registration methods available with MeVisLab. MeVisLab is open source software as a rapid prototyping and development platform for medical image processing and visualization. It runs on Windows, Linux, and Mac OS X. The developers of MERIT module have provided an example network with brain MRI image as both the reference and template image to start experiment with the registration methods. The objective of this study was to optimize the value of MERIT module parameters for positron emission tomography/computed tomography (PET/CT) image registration. Materials and Methods: One whole-body PET/CT reconstructed image data set in DICOM format and its registered images in JPEG format were exported from nuclear medicine processing terminal. These images were used for optimization of the value of MERIT module parameters. All experiments were performed on MEVISLAB installed on personal computer. One by one default value of parameters was changed, and the registered PET/CT images were visually compared with registered PET/CT images from nuclear medicine processing terminal. Whole-body PET/CT image data set of 50 patients was used to validate the optimized value of MERIT module parameters. Results and Conclusion: All 50 image data sets were successfully registered with optimized value of parameters, and the registered images with MERIT were visually equal to the registered images from nuclear medicine terminal. In SetworldMatrix tab, withSource image matrix = ignore, Reference image matrix = Forward and Elementary transform = ignore improved both accuracy and speed of the registration. The optimized value of parameters were found to be: In SetworldMatrix tab, source image matrix = ignore, Reference image matrix = Forward, and Elementary transform = ignore, with all other parameters as default value available in example network.
| PV68: Patient's feedback analysis: to assess the patient's experience and quality check at nuclear medicine department | | |
Nisha Bhatia, Saumya Kumari, Meenakshi Devri
Department of Nuclear Medicine, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
Background and Objectives: The ideal patient experience is built on clinical and nonclinical factors such as convenience, communication with doctors and staff, hospital environment (cleanliness and quietness), staff attitudes, and overall rating of the department. The measurement of patient satisfaction is an important quality indicator to assess the quality of hospital and its departments. The aim of this study was to assess the patient's experience and check the service quality of nuclear medicine department. Materials and Methods: The study was conducted with an easy to complete questionnaire consisting of 12 multiple-choice questions categorized into four different sections (i.e., relating to cleanliness, relating to time management, information about procedure and radiation safety, overall experience at nuclear medicine department). Feedbacks were collected from a total of 117 patients. All 12 questions were scored over point scale 4–1 (i.e., 4: excellent, 3: good, 2: average, 1: poor) to capture the level of satisfaction of patients underwent radionuclide scan at Nuclear Medicine Department of Cancer Research Institute. Results: Findings showed that percentage score for four different sections were as follows: relating to cleanliness 85.6%, relating to time management 93%, information about procedure and radiation safety 96.4%, and overall experience at nuclear medicine department 97.2%. Out of 12 aspects rated, for “overall experience” was rated best followed by “information provided about procedure and radiation safety.” The lowest ratings were received for “cleanliness of toilets” and “accessibility to department (sinages).” Conclusion: The patient feedback analysis is an important tool to know the satisfaction level of the patients and can be used as a tool for improving the services and care delivered. These analyses are helpful in building trust between staff and patients. Moreover, we can also access that whether the patient and their attendants have fully understood the instructions given to them about radiation safety measures or not. We feel that nuclear medicine workers should also focus on the importance of the patient's feedbacks, their analysis, and use of the same for improving the service quality and radiation safety measures for patients and their attendants.
| PV69: Normalized glomerular filtration rate in females using different Body surface area formulas | | |
Sarika, Ajay Kumar, Sangam Sood, Anish Bhattacharya
Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India
Background and Objectives: Plasma clearance of technetium-99m-diethylene-triaminepentaacetic acid (99mTc-DTPA) (gold standard technique) has been used for determining glomerular filtration rate (GFR). However, the guidelines require normalization of GFR for body surface area (BSA), particularly in females in whom the effects of BSA normalization have the largest consequences. Materials and Methods: A total of 62 female patients (age 47.4 ± 11 years) referred to our department for plasma sampling GFR study were included in the present study. A comparison of effect on GFR in females using different BSA calculating formulas was studied. The BSA calculated using nomogram was considered as reference BSA value for normalization. All GFR values were normalized using eight different BSA formulas (namely, Du Bois, Mesteller, Haycock, Grehan and George, Mehra, Fujimoto, Takahira, and Schlich [female]) and compared with the reference GFR and normalized GFR value. Results: The mean GFR was 87.47 ± 24.72 ml/min and normalized GFR was 94.40 ± 25.10 ml/min/1.73 m2. The mean normalized GFR values using Du Bois, Mesteller, Haycock, and Grehan and George formula were 94.06, 92.88, 92.20, and 91.81 ml/min/1.73 m2, respectively. The mean normalized GFR values using Mehra, Fujimoto, Takahira, and Schlich (female) formula were 94.62, 96.25, 93.32, and 99.88 ml/min/1.73 m2, respectively. The results from one way ANOVA and Bland–Altman agreement analysis showed that the all BSA formulas produced statistically similar results to the nomogram normalized GFR method. Furthermore, more than 96.0% of all GFR values from various methods were found to be within the 95.0% confidence interval of the reference value. However, all BSA formulas significantly overestimated the GFR in Indian females compared to the nonnormalized GFR values. Conclusion: Our results showed that all BSA correcting formulas yielded similar normalized GFR values in the females as compared to the nomogram normalized GFR values but significantly overestimated the nonnormalized GFR. Thus, any of the above formulas may be used with caution for normalizing the GFR values in Indian females.
| PV70: Education and training of nuclear medicine technology in India | | |
Srikanth Saminathan, S. C. Kheruka, Sanjay Gambhir
Department of Nuclear Medicine, SGPGIMS, Lucknow
Background and Objectives: This article describes importance, history, current situation, development, and current problems of academic and training courses of nuclear medicine technology (NMT) professionals (nonmedical) in India. Importance of Nuclear Medicine Technology Education and Training: NM is sophisticated profession and offers large diversity of diagnostic and therapeutic procedures, which often play a central role in patient management. At the same time, the field is constantly evolving with new procedures being continuously introduced. In such a rich and developing scenario, adherence to the best practice guidelines becomes crucial to offer for best patient care. The continuous developments in technology, instrumentation, radiopharmaceuticals, and innovative procedures make it one of the most rapidly evolving healthcare professions. With such continuing developments and innovation, best-practice may become a moving target appropriate education to the professionals. Most of the procedures performed by NM technical professionals in NM include diagnosis and therapy. To offer best practice, appropriate education and training are essential. The education process assures that NM technologists have the knowledge, skills, and judgment in their highly specialized discipline. In addition, lifelong learning is a core value for all healthcare professions. Therefore, entry-level education in NM must be sufficient. History of Training and Courses in India: Before 1973, the technicians in NM not having any degree or diploma in the filed they were sent for training followed by examination then made qualified technologist by the AERB. The first academic course started in 1973–1974 in Radiation Medicine Center, Mumbai, in the name of DMRIT which is now affiliated to Homi Baba University, Mumbai. The first PG course stared in AIIMS, New Delhi, and UG course by Manipal University, respectively, M. Sc. NMT and M. Sc. NMT. Current Situation and Development: There are four types of training courses currently agreed by competent authority (AERB):
- UG-DEGEREE
- PG-DEGREE
- PG-DIPLOMA
- M-TECH.
Problems and Challenges of Training and Courses of Nuclear Medicine Technology: Within India, there is a lack of following facts:
- Nonhomogenous nomenclature of course
- Different curricula/syllabus
- Different entry qualifications
- Insufficient basic facilities in some training institutions
- Insufficient faculties available many training intuitions
- Nonprior approval for the course
- Insufficient training period (1 year)
- RSO certification issues.
Conclusion: To establish best educational curriculum and same pattern of homogenous course, entry qualifications and minimum facilities of training institute should be considered by forming committee from various organizations such as AERB, SNMI, ANMPI, and NMPAI.
| PV71: Concept extraction from radiology reports of lung carcinoma cases using an open source medical terminology annotator: A feasibility study | | |
M. Sneha1, Ashish K. Jha, Umesh B. Sherkhane, Vinay Jaiswar, R. V. Prasad1, Carlos M. Ortiz2, Sander Puts3, Venkatesh Rangarajan, Andre Dekker4, Leonard Wee4
Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, 1Philips Innovation Campus, Philips India, Bengaluru, Karnataka, India, 2Netherlands eScienceCenter, Amsterdam, 3GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, 4Department of Radiation Oncology (MAASTRO Clinic), Maastricht, Netherlands
Background and Objectives: Unstructured natural language text is omnipresent in the electronic health records system and currently represents the second-largest volume of unstructured data in radiology departments. While this form of “big data” has tremendous potential for learning clinical insights, manual extraction of information from such records is laborious and time-consuming. Automated natural language processing (NLP) systems have been proposed that could potentially reduce workload and accelerate knowledge mining from radiology reports. In this study, we consider whether it is feasible to apply a linguistic-based approach, using a medical terminology annotator, to detect significant concepts relating to lung cancer diagnosis in a corpus of free text reports. Materials and Methods: We sampled 20 expert-generated free text radiology reports of computed tomographic (CT) scans from Tata Memorial Hospital performed on lung carcinoma patients. The reports were anonymized and cleaned to extract only the findings and impression using Python. We used cTAKES analysis engine AggregatePlainTextFastUMLS to extract the concepts of the terms using concept unique identifiers from the reports and also extracted the part-of-speech (POS) tagging based on the Penn Treebank Project. We specifically looked at recall (sensitivity) and accuracy of detecting reporting containing a list of keywords such as right upper lobe, left lower lobe, left lung, left upper lobe, middle lobe, NSCLC, and carcinoma. The results were then manually validated by a human reader to investigate early feasibility of the cTAKES tool for NLP, right lower lobe, and right lung. Results: The recall and accuracy for concept extraction were highest, i.e., 1, for words such as “left upper lobe,” “middle lobe,” “right lung,” “and left lung,” “carcinoma.” The recall and accuracy for “right lower lobe” were 0.9 and 0.818, respectively. For “left lower lobe,” both recall and accuracy were 0.85, and for “nonsmall cell lung carcinoma (NSCLC),” the values were 0.8. There were too few instances of “right lower lobe” found out of 20, to properly estimate recall and accuracy. The POS tags for words such as “lobe,” “lung,” “NSCLC,” and “carcinoma” were rightly tagged as noun phrases and words such as “right,” “left,” “upper,” “lower,” and “middle” were tagged as adjectives phrases. Conclusion: TAKESPOS tagging and entity recognition in the above feasibility study is a good foundation but still lacks high performance to be used for identifying extractable target information about lung cancer from radiology reports. Future work will investigate the combination of POS tagging and concept identification together with word embeddings in a vector-based approach.
| PV72: Dosimetry in metastatic castration-resistant prostate cancer patients treated with 177Lu-prostrate-specific membrane antigen-617: Some observations | | |
Kamaldeep, Gaurav Wanage1, Sudeep Kumar Sahu1, Pravind Maletha1, Sonam Suman1, Sandip Basu, Tapas Das, Sharmila Banerjee
Division of Radiation Safety System, BARC, Homi Bhabha National Institute, 1Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Background and Objectives: Prostate cancer is the second most common diagnosed cancer among men worldwide. Targeting of prostate-specific membrane antigen (PSMA) overexpression in prostate cancer with 177Lu-labeled PSMA-ligands presents a promising option to treat the cancer patients suffering from prostate cancer. This therapeutic modality is used in Radiation Medicine Centre for the treatment of metastatic castration-resistant prostate cancer (mCRPC), for the last 1 year. The objective of this study was to perform image-based absorbed dose calculations for tumor lesions and dose-limiting organs in a small cohort of mCRPC patients during the first cycle of therapy, and this will enable us to decide about the optimal treatment protocol. Materials and Methods: Ten patients (64.1 ± 8.96 years) with a history of prostate cancer, proven by histopathological studies and radiological findings, underwent radiotherapeutic treatment with 177Lu-PSMA-617 and were enrolled for this prospective study. The 177Lu-PSMA-617 activity administered in each patents varied from 4.51 to 5.66 GBq with a mean ± standard deviation of 5.02 ± 0.42 GBq. All patients underwent whole-body γ-scintigraphy (anterior and posterior planar acquisitions) at 0.5 (prevoid), 2, 12, 24, and 72/96 h (postvoid) after the administration of therapeutic dose of 177Lu-PSMA-617. During each whole-body γ-scintigraphy, a source of 177Lu with known activity was used as the reference standard required for dosimetry calculations. All five scans were compared and region of interest (ROI) was drawn anterior and posterior over the standard source, whole-body, kidney, liver, spleen, lacrimal glands, salivary glands, and tumors. From each ROI, the amount of radioactivity retained in the patient's respective organ/tumor was calculated. From the retained activity statistics and thus number of disintegrations in the organ/tumor, absorbed doses were estimated by using OLINDA 2.0 software. Results: The mean absorbed dose ± SD per unit activity determined were as follows: salivary gland (0.63 ± 0.32 [range 0.22–1.12] Gy/GBq), lacrimal gland (0.42 ± 0.23 [range 0.09–0.86] Gy/GBq), kidney (0.76 ± 0.18 [range 0.44–1.02] Gy/GBq), liver (0.09 ± 0.04 [range 0.05–0.18] Gy/GBq), and spleen (0.31 ± 0.10 [range 0.18–0.47] Gy/GBq). The calculated mean absorbed dose per unit activity to the tumor lesions (n = 32) averaged for all patients was 5.73 ± 8.77 (range 0.2–33.89) Gy/GBq. Conclusion: In the present study, we report our first dosimetry data with 177Lu-PSMA-617 in patients with advance mCRPC. The results obtained are comparable to the reports published in the contemporary literature.
| PV73: To compare the reconstruction method with ordered-subset expectation maximization 2D and FLASH 3D using Chang's attenuation correction for Tc99m Trodat-1 image (BRIT TRODAT KIT is used for imaging) | | |
S. Dinesh Kumar, Raman Kumar Joshi, R. Gopinath, Chandana, Pardeep Kumar, A. K. Gupta
Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
Introduction: Parkinson's disease (PD) is a neurodegenerative disease due to progressive loss of dopaminergic neurons in the basal ganglia. Single photon emission computed tomography (SPECT) scans using [99mTc]TRODAT-1 has been used to image DAT concentration. The image quality of SPECT scans depends on the imaging and reconstruction parameters. Imaging and reconstruction procedure for [99mTc]TRODAT-1/SPECT are essential to obtain diagnostic accuracy of dopamine-related diseases. Objective: Comparison between two different iterative reconstruction method processing method of TRODAT-1 scan using Chang's attenuation correction – Ordered-Subset Expectation Maximization (OSEM) 2D versus OSEM reconstruction method with 3D collimator beam modeling (FLASH 3D). Methods: Tc99m TRODAT 20 ± 5 mCi was injected into the patients. After 4 h postinjection, patients were placed in supine position with head first orientation and head is fixed with head-holder in SIEMENS Symbia T6 SPECT CT scanner. SPECT scan of the brain was acquired with the following imaging parameters 60 s per projection for 64 projections in step and shoot method in noncircular orbit, matrix of 128 × 128 and Zoom 1.23. CT of the brain also acquired with 130 kV, effective 250 mAs (Care dose 4D) in the same position of the patient. Data reconstruction was performed in SPECT CT console with Syngo esoft software using two different reconstruction parameters, OSEM 2D (8 iteration 8 subset and 6 iteration 16 subset) and FLASH 3D (8 iteration 8 subset and 6 iteration 16 subset) using Gaussian filter with full width half maximum 8 mm. All the data set was corrected for photon attenuation using Chang's first-order correction with attenuation coefficient of 0.12/cm applied manually for all projection angles. After reconstruction, the two set of reconstructed images were compared visually to assess for resolution of striatal structures of the TRODAT SPECT. Results: On visual analysis, it was found that using FLASH 3D and Chang's attenuation correction having slightly superior resolution then OSEM 2D. Conclusions: FLASH 3D-reconstructed images with 6 iteration 16 subset considerably improve resolution and delineation of striatal structures. This would be also be used in centers with only Gamma Camera facility.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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