Correlation of 68Ga-PSMA-11 PET/CT biodistribution with PSMA expression by immunohistochemistry in patients with HCC: A pilot prospective monocentric study.

PURPOSE: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with limited diagnostic and prognostic tools beyond conventional imaging modalities such as CT and ceMRI. Prostate-specific membrane antigen (PSMA) expression, observed in the neoangiogenic endothelial cells of HCC, has emerged as a potential target. This study evaluated the correlation between PSMA biodistribution using [68Ga]Ga-PSMA-11 positron emission tomography (PSMA PET/CT) and PSMA expression by immunohistochemistry (IHC) in surgical HCC patients. Secondary aim was to assess the diagnostic performance of PSMA PET/CT in this prospective cohort. METHODS: This prospective monocentric study enrolled patients with suspected HCC undergoing curative-intent liver resection or transplantation. All participants underwent ceMRI and [68Ga]Ga-PSMA-11 PET/CT within a 3-month interval, with imaging results correlated to postoperative histopathology and IHC for PSMA expression. Semi-quantitative PET parameters were analyzed alongside tumor grade, vascular invasion, and IHC metrics. RESULTS: Eligible patients were 39, of those 31 were treated surgically. 27/31 (87%) showed PSMA uptake on PET/CT, with a median SUVmax of 12.6 (IQR10.2-16.5). According to IHC intensity analysis, PSMA was expressed in 22/24 (91.6%) of HCC. High PSMA uptake correlated with strong PSMA expression in tumor-associated vasculature (p = 0.028). No significant correlations were found between PET parameters and histological features, such as Edmondson grade or vascular invasion (p > 0.05). CONCLUSIONS: PSMA PET/CT offers robust diagnostic accuracy for HCC and correlates with vascular PSMA expression, suggesting potential utility in preoperative staging. These findings support the further exploration of PSMA imaging as a biomarker for HCC.