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Year : 2021  |  Volume : 36  |  Issue : 1  |  Page : 90-91  

68Ga-prostate-specific membrane antigen uptake as a surrogate biomarker of neovascularity in hepatocellular carcinoma

1 Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
2 Kuwait Cancer Control Centre, Shuwaikh, Kuwait

Date of Submission24-Feb-2020
Date of Decision28-Mar-2020
Date of Acceptance30-Mar-2020
Date of Web Publication04-Mar-2021

Correspondence Address:
Dr. Najeeb Ahmed
Jack Brignall PET/CT Centre, Hull and East Yorkshire Hospitals NHS Trust, Hull
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijnm.IJNM_38_20

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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 7];36:90-1. Available from:

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.[1] However, 68Ga-PSMA uptake has been reported in solid malignant tumors including breast cancer, HCC, and renal cell carcinoma[2],[3],[4] and is thought to be in tumoral microvessels.[5] Preliminary data indicate that the detection rate of 68Ga-PSMA PET-CT is superior to 18F-FDG in HCC.[6] A recent study by Tolkach et al.[7] 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.[8],[9]

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.[10] Unsurprisingly, the typical pattern of enhancement on CECT imaging in HCC has been shown to correlate with microvessel density.[11] 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,[12],[13] 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.

   References Top

Asman Y, Evenson AR, Even-Sapir E, Shibolet O. [18F] fludeoxyglucose positron emission tomography and computed tomography as a prognostic tool before liver transplantation, resection, and loco-ablative therapies for hepatocellular carcinoma. Liver Transpl 2015;21:572-80.  Back to cited text no. 1
Demirci E, Ocak M, Kabasakal L, Decristoforo C, Talat Z, Halaç M, et al. (68) Ga-PSMA PET/CT imaging of metastatic clear cell renal cell carcinoma. Eur J Nucl Med Mol Imaging 2014;41:1461-2.  Back to cited text no. 2
Sasikumar A, Joy A, Nanabala R, Pillai MR, Thomas B, Vikraman KR. 68Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2016;43:795-6.  Back to cited text no. 3
Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 2014;14:26.  Back to cited text no. 4
Kesler M, Levine C, Hershkovitz D, Mishani E, Menachem Y, Lerman H, et al. 68Ga-PSMA is a novel PET-CT tracer for imaging of hepatocellular carcinoma: A prospective pilot study. J Nucl Med. 2019;60:185-191. doi:10.2967/jnumed.118.214833.  Back to cited text no. 5
Taneja S, Taneja R, Kashyap V, Jha A, Jena A. 68Ga-PSMA Uptake in Hepatocellular Carcinoma. Clin Nucl Med 2017;42:e69-e70.  Back to cited text no. 6
Tolkach Y, Goltz D, Kremer A, Ahmadzadehfar H, Bergheim D, Essler M, et al. Prostate-specific membrane antigen expression in hepatocellular carcinoma: Potential use for prognosis and diagnostic imaging. Oncotarget 2019;10:4149-60.  Back to cited text no. 7
Conway RE, Petrovic N, Li Z, Heston W, Wu D, Shapiro LH. Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction. Mol Cell Biol 2006;26:5310-24.  Back to cited text no. 8
Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res 1999;59:3192-8.  Back to cited text no. 9
European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182-236.  Back to cited text no. 10
Muto J, Shirabe K, Sugimachi K, Maehara Y. Review of angiogenesis in hepatocellular carcinoma. Hepatol Res 2015;45:1-9.  Back to cited text no. 11
Ahmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177 Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget 2016;7:12477-88.  Back to cited text no. 12
Rahbar K, Bode A, Weckesser M, Avramovic N, Claesener M, Stegger L, et al. Radioligand therapy with 177 Lu-PSMA-617 as a novel therapeutic option in patients with metastatic castrationresistant prostate cancer. Clin Nucl Med 2016;41:522-8.  Back to cited text no. 13


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