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

⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA), a PET tracer that was recently introduced for the imaging of prostate cancer, may accumulate in other solid tumors, including hepatocellular carcinoma (HCC). The aim of this study was to assess the potential role of ⁶⁸Ga-PSMA PET/CT in the imaging of HCC. Methods: Included in this prospective pilot study were 7 patients who had HCC with 41 liver lesions: 37 suspected malignant lesions (tumor lesions) and 4 regenerative nodules. For each liver lesion, the uptake of ⁶⁸Ga-PSMA and the uptake of ¹⁸F-FDG were measured (as SUV and lesion-to-liver background ratios [TBR-SUV]) and correlated with dynamic characteristics (Hounsfield units [HU] and TBR [TBR-HU]) obtained from contrast-enhanced CT data. Immunohistochemical staining of PSMA in the tumor tissue was analyzed in samples obtained from 5 patients with HCC and compared with that of control samples obtained from 3 patients with prostate cancer. Results: Thirty-six of the 37 tumor lesions and none of the regenerative nodules showed increased ⁶⁸Ga-PSMA uptake, and only 10 lesions were ¹⁸F-FDG–avid. On the basis of contrast enhancement, tumor lesions were categorized as 27 homogeneously enhancing lesions, 9 lesions with “mosaic” enhancement (composed of enhancing and nonenhancing regions in the same lesion), and a single nonenhancing lesion (the only non–⁶⁸Ga-PSMA–avid lesion). The Mann–Whitney test revealed that ⁶⁸Ga-PSMA uptake was significantly higher in enhancing tumor areas than in nonenhancing areas and, in contrast, that ¹⁸F-FDG uptake was higher in nonenhancing areas (P < 0.001 for both). ⁶⁸Ga-PSMA uptake (TBR-SUV_max) was found to correlate with vascularity (TBR-HU) (Spearman r, 0.866; P < 0.001). Immunohistochemistry showed intense intratumoral microvessel staining for PSMA in HCC; in contrast, cytoplasmic and membranous staining, mainly in the luminal border, was seen in prostate cancer samples. In 2 of the study patients, ⁶⁸Ga-PSMA PET/CT identified unexpected extrahepatic metastases. The 4 regenerative liver nodules showed no increased uptake of either PET tracer. Conclusion:⁶⁸Ga-PSMA PET/CT was superior to ¹⁸F-FDG PET/CT for imaging patients with HCC. HCC lesions are more commonly hypervascular, taking up ⁶⁸Ga-PSMA in tumoral microvessels. ⁶⁸Ga-PSMA PET/CT is a potential novel modality for imaging patients with HCC.