Correlation of [ ⁶⁸ Ga]Ga-PSMA-11 PET biodistribution with immunohistochemical PSMA expression in hepatocellular carcinoma: Results from the prospective study MORE-PSMA.

e16326 Background: Hepatocellular carcinoma (HCC) is challenging to diagnose beyond CT and MRI. Prostate-specific membrane antigen (PSMA), a known marker in prostate cancer, is also expressed in the neoangiogenic endothelial cells of HCC and may serve as a novel imaging target. The MORE-PSMA is a prospective study aimed to investigate the correlation between [ 68 Ga]Ga-PSMA-11 PET/CT (PSMA-PET) uptake and PSMA expression by immunohistochemistry (IHC) in HCC patients undergoing surgery. Secondary aim was to evaluate the diagnostic accuracy of PSMA-PET compared to contrast-enhanced MRI (ceMRI). Methods: Eligibility criteria included: suspected HCC on ceMRI; suitability for liver resection (LR) or liver transplant (LT); age ≥ 18 years and no previous systemic therapies. PSMA-PET and ceMRI results were compared with histopathological findings from surgical specimens, including Edmondson-grading, IHC analysis of PSMA-positive cells, and a composite immunoreactive score (IRS) was calculated. Sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of PSMA-PET were assessed using pathology as reference. Results: Of the 39 patients initially screened, 9 were excluded (increased surgical risk, higher tumor burden or refusal of surgery). Among the 30 HCC patients included, the median age was 66 years (interquartile range [IQR] 73 - 58 years), with a median bilirubin of 1.2mg/dL (IQR 2.3 – 0.7), alpha--fetoprotein 4.4 ng/mg (IQR 68 – 2.6), albumin 4 g/dL (IQR4.5 – 3.5), positive under liver disease (ULD) in 87.5% cases. HCC was confirmed in 24/30 (80%) , all of whom demonstrated significant uptake on PSMA-PET (p. value 0.03) with a median SUVmax of 12.0 (IQR 7.3–14.9). High PSMA uptake on PET correlated with strong PSMA expression in tumor-associated vasculature on IHC (p = 0.028).No IHC expression was observed in tumor cells. PSMA-PET demonstrated a sensitivity of 100%, NPV of 100%, and comparable PPV to ceMRI (85.7% vs. 82.1%). No significant correlation was observed between PSMA-PET parameters and histological features such as Edmondson grade or vascular invasion. At follow-up, 21/24 (87.5%) remained disease-free on imaging and laboratory. Conclusions: PSMA-PET correlates strongly with vascular PSMA expression and demonstrates excellent diagnostic performance for HCC, supporting its potential role in preoperative staging. Its high sensitivity and NPV may aid in optimizing patient selection for liver surgery/transplantation. Further studies are warranted to explore its implications in therapeutic planning and monitoring, especially those targeting tumor neovasculature.