Background: Chemokine receptor CXCR4 is overexpressed in more than 27 different human tumors that make it a promising target in oncology. Ga-68 Pentixafor is the most promising positron emission tomography tracer for imaging CXCR4 receptors; hence, the present study was carried out to optimize the radiosynthesis of Ga-68-Pentixafor using fully automated method and the quality control (QC) checks were performed before being used as a clinical product. We also studied the normal biodistribution pattern of Ga-68-pentixafor intended for the use in variety of malignancies. Materials and Methods: We optimized the automated radio-synthesis of Ga-68 Pentixafor under good manufacturing practice conditions. A total of 62 productions were carried out in a span of 4 years. Extensive QC tests were performed to check for potency, identity, efficacy, and stability of the tracer. Biodistribution of Ga-68 Pentixafor was investigated in a healthy volunteer to determine normal range of standardized uptake value_maximum (SUV_max) values in various organs. Results: The radiotracer was prepared successfully in 57/62 productions with radiochemical purity of >99%. Mean radiolabelling efficiency of 73.1% ± 7.7% (n = 57) was obtained with synthesis time approximatively of 34 min. The radiolabeled complex showed no signs of dissociation up to 4 h at the room temperature. Ga-68 Pentixafor upon incubation with human serum was found to be stable at 37°C for 4 h. The highest normal organ uptake was seen in urinary bladder (SUV_mean = 146.0), spleen (SUV_mean = 6.80) followed by kidneys (SUV_mean = 4.99). Conclusion: Using the automated radiosynthesis, Ga-68 Pentixafor exhibited good radiolabelling efficiency with excellent in vitro and in vivo stability and favorable biodistribution showing clinical applicability of the tracer.

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Introduction: We carried out this study to compare the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) and gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68 PSMA PET/CT) to detect prostatic carcinoma in patients with serum prostate-specific antigen (PSA) between 4 and 20 ng/ml in prebiopsy setting. Materials and Methods: This prospective study evaluated men with serum PSA values between 4 and 20 ng/ml. All patients underwent mpMRI and Ga-68 PSMA PET/CT, followed by 12-core transrectal ultrasonography (TRUS)-guided biopsy to detect prostatic carcinoma. The diagnostic accuracy of mpMRI and PSMA PET/CT scan was compared with histopathological findings. Results: There were thirty patients included in the study with a median age of 73 years (age range: 69–79 years). The median total serum PSA was 8.0 ng/ml (5.0–19.9 ng/ml). Of these, 18 had an identifiable lesion on imaging and had histopathological findings suggestive of carcinoma prostate. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI were 100%, 92.30%, 94.73%, and 100%, respectively, and that of PSMA PET scan were 94.44%, 100%, 100%, and 92.31%, respectively. The diagnostic accuracy of both was 96.67%. Conclusion: PSMA PET scan showed higher PPV and specificity while mpMRI showed higher sensitivity and NPV. The accuracy in predicting presence of carcinoma was the same for both. PSMA PET showed higher specificity and PPV and predicted the subsequent need of biopsy. In our study, the NPV of PET, though good, was lower than mpMRI. Prospective trials with larger sample size are needed. In combination, PET/MRI may achieve greater accuracy and may serve as investigation of choice.

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Objective: Our study aims to establish the potential for tumor heterogeneity evaluated using ¹⁸F fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) texture analysis in nonsmall-cell lung carcinoma (NSCLC) patients who underwent platinum-based chemotherapy to provide an independent marker for overall survival (OS) of more than 1-year. Materials and Methods: A total of 42 patients (34 male and 8 female) with biopsy-proven NSCLC and mean age 55.33 ± 10.71 years who underwent a baseline F-18 FDG PET/CT and received platinum-based chemotherapy as first-line treatment were retrospectively included in the study. Ten first order, 21 s order texture parameters and 7 SUV and metabolic tumor volume (MTV) based metabolic parameters were calculated. All these parameters were compared between the two survival groups based on OS ≥1 year and OS <1 year. Cut-offs of significant parameters were determined using receiver operating characteristic curve analysis. Survival patterns were compared by log-rank test and presented using Kaplan-Meier curves. Cox proportion hazard model was used to determine the independent prognostic marker for 1 year OS. Results: In univariate survival analysis, 3 first order texture parameters (i.e. mean, median, root mean square with hazard ratios [HRs] 2.509 [P = 0.034], 2.590 [P = 0.05], 2.509 [P = 0.034], respectively) and 6 s order texture parameters (i.e. mean, auto correlation, cluster prominence, cluster shade, sum average and sum variance with HRs 2.509 [P = 0.034], 2.509 [P = 0.034], 3.929 [0.007], 2.903 [0.018], 2.954 [0.016] and 2.906 [0.014], respectively) were significantly associated with 1 year OS in these patients. Among the metabolic parameters, only metabolic tumor volume whole-body was significantly associated with 1 year OS. In multivariate survival analysis, cluster prominence came out as the independent predictor of 1 year OS. Conclusion: Texture analysis based on F-18 FDG PET/CT is potentially beneficial in the prediction of OS ≥1 year in NSCLC patients undergoing platinum-based chemotherapy as first-line treatment. Thus, can be used to stratify the patients which will not be benefitted with platinum-based chemotherapy and essentially needs to undergo some other therapy option.

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Neuroblastoma is the most common pediatric extracranial solid tumor. High-risk neuroblastoma is the most frequent presentation with an overall survival of approximately 50%. ¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG) scintigraphy in the assessment of the primary tumor and its metastases at diagnosis and after chemotherapy is a cornerstone imaging modality. In particular, the bulk of skeletal metastatic disease evaluated with ¹²³I-mIBG at diagnosis and the following chemotherapy has a prognostic value. Currently, single-photon emission computerized tomography/computerised tomography (SPECT/CT) is considered a fundamental part of ¹²³I-mIBG scintigraphy. ¹²³I-mIBG SPECT/CT is a highly specific and sensitive imaging biomarker and it has been the basis of all existing neuroblastoma trials requiring molecular imaging. The introduction of SPECT/CT has shown not only the heterogeneity of the mIBG uptake within the primary tumor but also the presence of completely mIBG nonavid metastatic lesions with mIBG-avid primary neuroblastomas. It is currently possible to semi-quantitatively assess tracer uptake with standardized uptake value, which allows a more precise evaluation of the tracer avidity and can help monitor chemotherapy response. The patchy mIBG uptake has consequences from a theranostic perspective and may partly explain the failure of some neuroblastomas to respond to ¹³¹I-mIBG molecular radiotherapy. Various positron emission tomography tracers, targeting different aspects of neuroblastoma cell biology, are being tested as possible alternatives to ¹²³I-mIBG.

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Introduction: With advent of gallium-labeling somatostatin analogs and its evaluation under positron emission tomography–computed tomography, there has been a tremendous surge in its application. Gallium 68 can be made available either from onsite cyclotron production or in the form of ready-to-use ⁶⁸Ge/⁶⁸Ga generators. Wherein setting up and running of cyclotron amounts to huge investment and dedicated team, the ⁶⁸Ge/⁶⁸Ga generator has proved to be a better option and viable project. Moreover, due to long half-life of ⁶⁸Ge, i.e. 271 days, it enables the usage of generator for several months. The preparation of gallium-labeled peptides is much simpler in comparison to 18F radiochemistry, but the radiation exposure has always been an area of concern owing to high-energy annihilation photon of 511 keV. Materials and Methods: In this study, we share our experience of self-installation of ⁶⁸Ge/⁶⁸Ga generator during lockdown and the various steps involved in installation of fully automated peptide-labeling system in customized mini hot cell module, synthesis steps, and quality control steps of gallium-based radiopharmaceutical. Results: The installation was successfully completed with online assistance during the pandemic situation. The average elution yield met company specification (>80%), and ⁶⁸Ga-labeled peptides were prepared with high radiochemical purity (>95%). The overall exposure in single batch of production and quality control never exceeded 3 μSv as shielding was well-taken care of with customized mini hot cell. Conclusion: With the described experience and validation process, one can easily think of making an installation at his/her center and cater to the needs of society with a new radiopharmaceutical.

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Bone and soft-tissue tumors display a wide range of metabolic activity on flurodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT) imaging due to their varying histopathological features. Several benign tumors show high FDG uptake similar to that seen in malignant lesions and their metabolic characteristics can overlap. Certain benign tumors can potentially undergo malignant transformation and FDG PET/CT can play an important role in detecting malignant change. The intensity of metabolic activity on FDG PET/CT correlates with histological grade of malignant tumors and also acts as a valuable prognostic factor. FDG PET/CT plays an important role in the staging work up of bone and soft-tissue malignancies. It has been found to be superior to conventional imaging techniques primarily for detecting distant metastatic disease. Because of its ability to detect metabolic changes, FDG PET/CT is a very useful in assessing response to treatment. Metabolic response seen on FDG PET is a powerful surrogate marker of histopathological response to chemotherapy. The purpose of this article is to study the variable patterns of FDG uptake in tumors of the musculoskeletal system, describe the clinical utility of FDG PET/CT in predicting malignant change in benign tumors and discuss its role in staging, response assessment, and prognostication of malignant lesions.

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Objective: The objective of the study is to assess the physiologic uptake of testes in patients undergoing ¹⁸F-fluoro-2-deoxyglucose (FDG) position emission tomography/computed tomography (PET/CT) scans for various malignancies other than testicular malignancy. Materials and Methods: The testicular uptake of ¹⁸F-FDG expressed as the standardized uptake value (T) was measured on PET/CT images in 320 men with no known testicular pathology from July 2019 to March 2020 at Tata Main Hospital, Jamshedpur. The ratio of maximum standardized uptake value (SUVmax) of the testis (T) to SUVmax of muscle (M) T/M ratio and to SUVmax of the liver (L) T/L ratio was calculated using SUVmax of right adductor muscle and liver, respectively. Testicular volume was calculated with the measurements taken from the axial, coronal, and sagittal slices of CT images. The correlation of testicular uptake with age, blood serum glucose level, and testicular volume was also analyzed. Results: The mean age of 320 men was 57 ± 15 years (range: 10–94) and the mean blood glucose level was 107.7 ± 23.5 mg/dl (range: 64–175). Mean testicular SUVmax in 320 men was 2.48 ± 0.80 (range: 0.67–5.5). The mean testicular volume of 640 testes of 320 men was 18.80 ± 4.83 cm³ (range: 3.85–33.56 cm³). The mean values of (T/M) and (T/L) ratios in the studied population were 3.64 ± 1.21 (range: 1.08–5.58) and 0.97 ± 0.251 (range: 0.34–1.88), respectively. The laterality index (L − R/(L + R) ×2) in 320 men was 0.074 ± 0.050 (0.000–0.308). There was a minimal negative correlation between testicular SUVmax and age (r = −0.136, P = 0.15). Mild negative correlation was noted between T/M ratio and age (r = −0.291, P < 0.0001) and between T/L ratio and age (r = −0.182, P = 0.001) in the studied population. Conclusion: The physiological testicular FDG uptake (SUVmax) of testes was 2.48 ± 0.80 (0.67–5.5) among the Indian population in this study, which has a mild negative correlation with age.

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Aim: In a Nuclear Medicine department, the risk of external and internal contamination in radiation workers is much higher than in other medical radiation facilities. The risk associated with both types of contaminations should be quantified to estimate the radiation dose received by the personal. Here, we designed an in vitro model to see the impact of internal and external contamination of F-18 and Technetium-99 m (Tc-99 m) on DNA damages. Methodology: Chinese hamster lung fibroblast V79 was used for all of the experiments. Irradiation was performed internally and externally (scenarios activity is mixed with the cell line [Internal] and activity kept at 1 cm distance from cell line [external]) using two different diagnostic radioactive sources (Tc-99 m and F-18) of known quantity 37 MBq. Total cumulated activity (MBq-min) was calculated up to one half-life of sources for both internal and external setups. An alkaline single gel electrophoresis technique (comet assay) was used for DNA damage analysis. Olive tail moment (OTM) was used to characterize DNA damage. Results: We have not observed any significant difference (P > 0.05) in OTM between internal and external irradiation for cumulated activity presented before one half-life of both diagnostic isotopes. However, a significant difference in OTM was noted between internal and external irradiation for cumulated activity presented at one half-life of radioactive sources (P < 0.05). DNA damage with internal exposure was found to be 17.28% higher for F-18 and 23% higher for Tc-99 m than external exposure at one half-life of radioactive sources. Overall, we noted greater DNA damage in F-18 as compared to Tc-99 m. Conclusions: Our in vitro study practically demonstrated that internal contamination is more hazardous than external exposure.

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Background: To date, the use of sialic acid that are reported to be elevated during malignancy has been largely unexplored for tumor imaging. The purpose of the present study was to study the modeled stable conformers of n-acetyl neuraminic acid (Neu5Ac) and its radiolabeled conjugate (Tc-99m-Neu5Ac) through computational chemistry approach and its in-vitro bioevaluation in rat C6 cell lines. Materials and Methods: The Neu5Ac was radiolabeled with Tc-99m using stannous reduction method and the radiochemical purity of Tc-99m-Neu5Ac was determined by instant thin layer chromatography.A Cheminformatic study of Tc-99m-Neu5Ac was performed by using Marvin application of ChemAxon. Glioma cancer cells were taken to evaluate the cytotoxicity and binding efficacy of Tc-99m-Neu5Ac. Results: Cheminformatic studies exhibited that the most stable conformer of Tc-99m-Neu5Ac is 15 kcal/mol more stable energetically over least stable conformer. The radiochemical yield of Tc-99m labeled Neu5Ac was observed to be greater than 90%. Further, the radiolabeled complex (Tc-99m-Neu5Ac)exhibited specificity for C6 glioma with time and concentration dependent cytotoxicity. Conclusion: In conclusion, Tc-99m-Neu5Ac has the potential to be exploited as an in-vivo radionuclide probe for tumor imaging.

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Nonspecific uptake of prostate-specific membrane antigen (PSMA) on PSMA positron-emission tomography/computed tomography (CT) is normally encountered in benign conditions, which is detected on morphological changes on CT component. However, having a site of uptake without any CT finding is a rare occurrence. We herewith report one such rare case of a 66-year-old male with metastatic prostatic adenocarcinoma, who demonstrated an incidental finding of intense focal PSMA uptake in the lung parenchyma.

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Introduction: This study aimed to predict the dose absorbed by normal organs with neuroendocrine tumors for ¹³¹I using single photon emission computed tomography/computed tomography (SPECT/CT) images and Geant4 application for tomographic emission (GATE) simulation. Materials and Methods: Four to 5 whole-body planar scan series, along with one SPECT/CT image, were taken from four patients following ^99mTc-hynic-Tyr³-octreotide radiotracer injection. After image quantification, the residence time of each organ was calculated using the image analysis and the activity time curves. The energy deposit and dose conversion (S-value) were extracted from the GATE simulation for the target organs of each patient. Using the residence times and S-values, the mean absorbed dose for the target organs of each patient was calculated and compared with the data obtained from the standard method. Results: Very close agreement was obtained between the S-value of the self–organ irradiation. The mean percentage difference between the two methods (i.e. GATE and Medical Internal Radiation Dose [MIRD]) was 1.8%, while a weak agreement was observed for cross-organ irradiation. The percentage difference between the total absorbed doses by the organs was 2%. The percentage difference between the absorbed doses obtained for tumors and three considered normal organs estimated by the GATE method was slightly higher than the MIRD method (about 11% on average for tumors). Conclusion: Regardless of the small difference between the obtained results for the organs and absorbed doses of the tumors in the present study, patient-specific dosimetry by the GATE methods is useful and essential for therapeutic radionuclides such as ¹³¹I due to high cross-dose effects, especially for young adult patients, to ensure the radiation safety and increase the effectiveness of the treatment.

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A 63-year-old male presented with left scrotal swelling and the ultrasound showed a large heterogeneous mass consistent with a testicular malignancy. The patient underwent left-sided orchiectomy which showed diffuse large B-cell lymphoma. The patient was then referred for whole-body F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) imaging which showed multiple hypermetabolic foci extending along the left inguinal canal to the retroperitoneum and the left perinephric space, suggesting direct contiguous spread of the tumor along the gonadal vessels, a form of metastasis unique to primary testicular lymphoma, and demonstrated for the first time on FDG PET/CT imaging.

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A 59-year old female presented with a lump in the right breast for 6 months. She developed progressively increasing backache for 3 months. Magnetic resonance imaging spine was suggestive of hypointense heterogeneous signal intensity in multiple dorsal vertebrae (D3–D8) and suggestive of Pott's spine. Sonomammography suggested a lesion with irregular margin in the retro-areolar region. Fine-needle aspiration cytology was infiltrating duct carcinoma. Fluorodeoxyglucose (FDG) positron-emission tomography–computed tomography revealed mass in the right breast with axillary lymph node. FDG-avid lytic destructive contiguous lesion was noted in mid-dorsal vertebrae. Apart from it, FDG-avid lytic lesion was also noted in the right iliac bone. The patient underwent vertebral lesion biopsy consistent with metastatic breast carcinoma. This case report demonstrates rare contiguous involvement of multiple vertebrae masquerading Pott's spine.

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Neuroblastoma is the most common extracranial solid tumor in childhood developing from primitive neural crest cells. I-131-metaiodobenzylguanidine (MIBG) a norepinephrine analog is highly sensitive and specific to identify primary and distant metastatic sites. We report the case of a 2-year-old female child with progressively increasing abdominal distention. Computed tomography (CT) revealed a large mass lesion involving the right suprarenal region with no hepatic or lymph node metastasis. No obvious skeletal abnormality was detected on the whole-body skeletal survey and Tc-99 m-methylene diphosphonate bone scan to suggest metastasis. I-131-MIBG scintigraphy with single-photon emission computerized tomography-CT showed MIBG-avid primary tumor in a suprarenal location with bilateral lower limbs growth plate as the only site of metastasis.

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This pictorial essay depicts normal appearances, complications and residual or recurrent disease on fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) studies in the postsurgical and postprocedural setting, other than head and neck malignancy. Reading and reporting FDG PET/CT in this scenario is daunting due to the multiple confounding false positives seen during this period. This article which is the second part in this series will familiarize the readers with the normal appearance and pitfalls seen in FDG PET/CT studies in thoracic and abdominopelvic malignancies during the postoperative and postprocedural period so as to avoid misinterpretations.

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Benign metabolic uptake on fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) is not uncommonly seen after immunization. We report a case of 30-year-old man with Hodgkin's lymphoma who underwent two cycles of chemotherapy. Interim ¹⁸F-FDG PET/computed tomography demonstrated complete metabolic response of prior hypermetabolic bilateral supraclavicular and mediastinal lymph nodes. Although multiple new normal-sized hypermetabolic left axillary and subpectoral lymph nodes are noted, relevant history revealed COVID vaccine 7 days prior scan with mild FDG uptake at the left deltoid muscle. These new findings at the left axilla are likely related to recent vaccination. ¹⁸F-FDG PET uptake in the lymph nodes is not so uncommon after immunization; relevant history is very important especially in the phase of massive immunization to avoid false interpretation.

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Thyroglobulin-elevated negative iodine scan (TENIS) syndrome represents a significant diagnostic and therapeutic challenge. Highly sensitive imaging modalities are required to help in the localization of disease, treatment planning, and prognostication. When compared to other imaging modalities, F-18 fluorodeoxyglucose positron-emission tomography–computed tomography has superior sensitivity and specificity in localizing the disease in this subset of patients. Tumor thrombus of thyroid cancer extending into the great vein is a very rare occurrence and management criteria have not been well established yet. We present a case of TENIS syndrome with tumor thrombus in the superior vena cava.

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Glomerular filtration rate (GFR) is an important indicator of renal function. Many methods have been developed to determine GFR in clinical examinations. This study aims to correlate between radionuclide plasma sampling methods (single and double blood samples, in vitro methods) and in vivo Gate's method using ^99mTc-diethylene triamine penta-acetic acid (^99mTc-DTPA) renography. Materials and Methods: 43 patients underwent this study, including 31 renal donors (Group 1) and 12 patients with obstructive uropathy (Group 2). All patients were administered with a range of 5–7 mCi of ^99mTc-DTPA. Then, renography performed simultaneously after injection and GFR calculation followed by Gate's method. Blood samples were collected at 60- and 120-min postinjection, samples were counted by a thyroid uptake system, and GFR was calculated using a single plasma sample method (SPSM) and a double plasma sample method (DPSM). Results: The mean GFRs calculated by Gate's method in Groups 1 and 2 were 85.8 ± 18.2 ml/min and 118.4 ± 13.9 ml/min, respectively. Meanwhile, using the in vitro blood sampling methods (DPSM and SPSM), the mean GFRs in Group 1 were 73.8 ± 15.4 ml/min and 56.4 ± 20.9 ml/min, respectively, and in Group 2 were 116.8 ± 12.9 ml/min and 106.3 ± 18.5 ml/min, respectively. There is a high correlation between Gate's method and DPSM in two groups (r = 0.86 and 0.72, respectively), and a moderate correlation was found between Gate's method and SPSM in both groups (r = 0.49 and r = 0.37, respectively). The two in vitro methods (DPSM and SPSM) revealed that moderate correlation in both groups (r = 0.74 and r = 0.67, respectively) was observed. Conclusion: Renography is a simple method but considered inaccurate for GFR determination. However, in vitro plasma sampling is rarely used in Vietnam. In this study, Gate's method correlated well with DPSM and tended to overestimate GFR. Further, the in vitro methods can be applied to correct the in vivo method as a confirmatory test in some cases.

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We describe a rare case of osteogenic sarcoma of the right femur; who 2 years after the treatment of primary site developed dural metastasis. Surveillance imaging for unusual pattern of metastasis may lead to earlier detection and treatment decision-making, which may improve survival and quality of life.

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A 45-year-old male with a history of trauma was referred to the department of nuclear medicine to identify site of a biliary leak, which could not be identified in ultrasound and exploratory laparotomy. Contrast-enhanced computed tomography (CT) was able to identify lacerations in the right lobe of the liver, but the extent of injury to the biliary pathways and vessels was unclear. 99mTc-HIDA scintigraphy with single-photon emission CT/CT was not only able to identify the site of leak but also the extent of infarcted area.

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A 7-year-old male with a history of blunt trauma to the abdomen and diagnosis of perinephric hematoma in contrast-enhanced computed tomography (CT) presented with increasing peri-nephric collection (after ~1.5 months) in the serial ultrasound examinations. The patient was referred to the department of nuclear medicine for the assessment of this collection as well as renal function. In 99mTc-diethylenetriamine pentaacetate renal scintigraphy, progressively increasing radiotracer activity was noted inferolaterally to the left kidney, separated from the same by a photopenic area. Single-photon emission computed tomography/CT revealed a peri-nephric urinoma in relation to the previously diagnosed hematoma at the lower pole; which was communicating with the pelvi-calyceal system (PCS). Not only did the renal scintigraphy aid in the diagnosis of urinoma but it was also able to show that it was communicating freely with the PCS and that the rest of the renal parenchyma was functioning adequately. This multi-faceted assessment in a single investigation allowed clinicians to opt for the conservative management despite the increasing size of urinoma in the early follow-up.

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Thoracic aortic aneurysm (TAA) should be treated before the complications with prophylactic surgery. However, important number of ruptures have been occurred below the cut-off size for surgery. In addition, in some cases, who in the cut-off value limit, decision of surgery may sometimes be difficult. ¹⁸Fluoro-deoxy-glukose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) may useful such situations. We present a case that, TAA in ¹⁸FDG-PET/CT in a patient with larynx carcinoma. He had a TAA with near the cut-off value and increased metabolic activity in baseline imaging. After 3 months, SUV_max value increased and elective surgery was performed. We think that aneurysms may be another pathology that ¹⁸FDG-PET/CT potentially be useful apart from imaging malignant diseases.

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