|Year : 2021 | Volume
| Issue : 1 | Page : 90-91
68Ga-prostate-specific membrane antigen uptake as a surrogate biomarker of neovascularity in hepatocellular carcinoma
Samreen Muzaffar1, Najeeb Ahmed1, Uzma Rahman1, Fareeda Al Kandari2, Sharjeel Usmani2
1 Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
2 Kuwait Cancer Control Centre, Shuwaikh, Kuwait
|Date of Submission||24-Feb-2020|
|Date of Decision||28-Mar-2020|
|Date of Acceptance||30-Mar-2020|
|Date of Web Publication||04-Mar-2021|
Dr. Najeeb Ahmed
Jack Brignall PET/CT Centre, Hull and East Yorkshire Hospitals NHS Trust, Hull
Source of Support: None, Conflict of Interest: None
| Abstract|| |
68Ga-prostate-specific membrane antigen (68Ga-PSMA) is expressed in the endothelium of tumor-associated neovasculature of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 45-year-old man with known colorectal cancer, cirrhosis, and hepatitis C. Contrast-enhanced computed tomography (CT) showed a hypervascular lesion in the liver, and 18F-fluorodeoxyglucose positron emission tomography (PET) did not show any suspicious hepatic uptake. 68Ga-PSMA PET-CT showed predominantly heterogeneous perilesional uptake in a configuration similar to the arterial enhancement pattern on the diagnostic CT. 68Ga-PSMA uptake in hepatocellular carcinoma appears to be primarily neoangiogenesis driven, and its morphological and functional characterization can subsequently influence the selection of anti-neoangiogenic chemotherapy agents as well as guiding radionuclide ligand therapy.
Keywords: 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography, angiogenesis, hepatocellular carcinoma, positron emission tomography/computed tomography
|How to cite this article:|
Muzaffar S, Ahmed N, Rahman U, Al Kandari F, Usmani S. 68Ga-prostate-specific membrane antigen uptake as a surrogate biomarker of neovascularity in hepatocellular carcinoma. Indian J Nucl Med 2021;36:90-1
|How to cite this URL:|
Muzaffar S, Ahmed N, Rahman U, Al Kandari F, Usmani S. 68Ga-prostate-specific membrane antigen uptake as a surrogate biomarker of neovascularity in hepatocellular carcinoma. Indian J Nucl Med [serial online] 2021 [cited 2022 Dec 1];36:90-1. Available from: https://www.ijnm.in/text.asp?2021/36/1/90/310795
A 45-year-old male, with an established history of hepatitis C and colorectal cancer treated with surgery 2 years back, showed a hepatic mass on ultrasonography suspicious for metastases. Carcinoembryonic antigen was normal with high alpha fetoprotein values. Contrast enhanced computed tomography (CECT), demonstrated a large predominantly hypodense lesion in segment VII [Figure 1]i, [Figure 1]j, [Figure 1]k with enhancement of the lesion in the arterial phase and rapid washout during the delayed phase, i.e., appearances highly suspicious of hepatocellular carcinoma (HCC). A subsequent fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) was negative, however, a 68Ga prostate specific membrane antigen (PSMA) PET CT [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g, [Figure 1]h showed heterogeneous uptake related to the mass. This was predominantly in a peripheral distribution, i.e., in a configuration quite similar to the enhancement pattern seen on arterial phase of CECT. Subsequent biopsy of the lesion confirmed HCC.
|Figure 1: a) FDG MIP and b-d) Transaxial FDG PET-CT images show no abnormal FDG localization in the liver. Triple phase i) un-enhanced j) arterial and k) venous CT images showed a large predominantly arterial enhancing lesion in segment VII with imaging features of Hepatocellular Carcinoma (HCC) e) 68Ga-PSMA MIP f-h) Transaxial 68Ga-PSMA PET-CT images show heterogenous increase tracer uptake in segment VII in a peripheral pattern closely resembling pattern of enhancement on arterial phase imaging (j)|
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18F-FDG PET-CT has a limited role in HCC as only half of the cases are 18F-FDG avid. However, 68Ga-PSMA uptake has been reported in solid malignant tumors including breast cancer, HCC, and renal cell carcinoma,, and is thought to be in tumoral microvessels. Preliminary data indicate that the detection rate of 68Ga-PSMA PET-CT is superior to 18F-FDG in HCC. A recent study by Tolkach et al. reported that HCC has high levels of PSMA expression on tumor vessels and canalicular membrane of tumor cells. PSMA plays a major role in regulating angiogenesis and is expressed in the endothelium of tumor-associated neovasculature in these solid malignancies possibly due to tumor-derived angiogenic factors and endothelial cell sprouting.,
Our case highlights the advantage of 68Ga-PSMA PET-CT in comparison to 18F-FDG PET-CT in characterizing focal hepatic lesions suspicious of HCC. These morphological features on CECT are usually secondary to abnormal handling of contrast material by newly formed vessels in a malignant lesion. Unsurprisingly, the typical pattern of enhancement on CECT imaging in HCC has been shown to correlate with microvessel density. The most interesting aspect of the current images is that the arterially enhancing peripheral component of the index liver lesion displaying higher 68Ga-PSMA uptake indirectly reflects the positive correlation between increased 68Ga-PSMA and lesion neovascularity.
This observation also highlights the potential of 68Ga-PSMA PET-CT in guiding therapeutic options in HCC. This includes suitability and response assessment with antiangiogenic chemotherapy and as a potential guide to radionuclide legend therapy with α/β-emitters. Some recent studies have shown promising response rates of 177Lu- 617 PSMAtargeted radioligand therapy,, and in the future, PSMA-targeted radioligand therapies can also be considered for other cancers including HCC.
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Conflicts of interest
There are no conflicts of interest.
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