⁶⁸Ga-Labeled Prostate-Specific Membrane Antigen Is a Novel PET/CT Tracer for Imaging of Hepatocellular Carcinoma: A Prospective Pilot Study

Abstract

Ga-Prostate Specific Membrane Antigen (Ga-PSMA), a positron emission tomography (PET) tracer that was recently introduce for imaging of prostate cancer, may accumulate in other solid tumors including Hepatocellular Carcinoma (HCC). The aim of the study was to assess the potential role of Ga-PSMA PET-Computed Tomography (CT) for imaging of HCC. A prospective pilot study in seven patients with HCC with 41 liver lesions: 37 suspected malignant lesions (tumor lesions) and 4 regenerative nodules. For each liver lesion, uptake of Ga-PSMA andF-FDG uptake were measured [standard uptake value (SUV) and lesion-to-liver background ratios (TBR-SUV)], and correlated with dynamic characteristics (HU and TBR-HU) obtained on contrast enhanced CT data. Immunohistochemistry staining of PSMA in the tumor tissue was analyzed in samples obtained from 5 patients with HCC and compared to control samples from 3 patients with prostate cancer. Thirty-six of the 37 tumor lesions and none of the regenerative nodules showed increasedGa-PSMA uptake while only 10 lesions were F-FDG avid. Based on contrast enhancement, tumor lesions were categorized into 27 homogeneously enhancing lesions, nine lesions with "mosaic" enhancement composed of enhancing and non-enhancing regions in the same lesion and a single non-enhancing lesion, the latter being the only non-Ga-PSMA avid lesion. Using the Mann-Whitney test, Ga-PSMA uptake was found significantly higher in enhancing tumor areas compared to non-enhancing areas and in contrast,F-FDG uptake was higher in non-enhancing areas, P<0.001 for both. Ga-PSMA uptake (TBR SUV) was found to correlate with vascularity (TBR-HU) (Spearman r=0.866, p<0.001). Immunohistochemistry showed intense intra-tumoral microvessel staining for PSMA in HCC, in contrast with cytoplasmic and membranous staining, mainly in the luminal border, in prostate cancer samples. In two of the study patients Ga-PSMA PET-CT identified unexpected extrahepatic metastases. Four regenerative liver nodules showed no increased uptake of either of the PET tracers.Ga-PSMA PET-CT is superior to F-FDG PET-CT in imaging patients with HCC. HCC lesions are more commonly hypervascular taking upGa-PSMA in tumoral micro-vessels. Ga-PSMA PET-CT is a potential novel modality for imaging patients with HCC.

Prostate-specific membrane antigen expression in hepatocellular carcinoma: potential use for prognosis and diagnostic imaging

“…One of these tumors is hepatocellular carcinoma. Only several case reports to date highlighted PSMA positivity of hepatocellular carcinoma on PET/CT [7][8][9][10]. Therefore, we provide here the first comprehensive evaluation of PSMA expression in HCC, benign peritumoral tissue and benign liver tumors.…”

“…Some of these tumors have already been extensively characterized with regard to PSMA expression (kidney cancer, breast cancer, gastric cancer, colon cancer), others are still not addressed (hepatocellular carcinoma, endometrial cancer). Several case reports and one case series to date reported the positivity at PSMA positron emission tomography / computed tomography (PET / CT) in approximately 10 patients with a hepatocellular carcinoma (HCC) [7][8][9][10].…”

Incidental detection of primary hepatocellular carcinoma on 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography imaging in a patient with prostate cancer

“…[ 9 ] PSMA uptake has been randomly reported in cases of colon, esophageal, thyroid, lung, and liver cancers, intrahepatic cholangiocarcinoma, renal cell carcinoma, brain tumors, sarcoidosis, Paget bone disease, rib fractures, and so on. [ 10 – 12 ] Kesler M et al performed 68 Ga-PSMA PET/CT imaging on 41 lesions in 7 patients suspected of having HCC [ 13 ] and reported that 68 Ga-PSMA positivity was detected in 36/37 tumor lesions. They also found that none of the 4 regenerative nodules examined showed an increase in 68 Ga-PSMA uptake.…”

Radiolabelled PSMA PET/CT or PET/MRI in hepatocellular carcinoma (HCC): a systematic review

“…A total of 55 articles were extrapolated with the computer literature search and by reviewing the titles and abstracts 43 of them were excluded because the reported data were not within the field of interest of this review. Twelve articles were selected and retrieved in full-text version [22][23][24][25][26][27][28][29][30][31][32][33]; one additional study was found screening the references of these articles [34]. A total of 13 articles were then included in the systematic review [22][23][24][25][26][27][28][29][30][31][32][33][34] (Fig.…”