Diagnostic Performance of PSMA PET/MRI in Characterizing LI-RADS 3 Observations in Patients with Cirrhosis

Liver Imaging Reporting and Data System (LI-RADS) category 3 (LR-3) observations remain indeterminate and often result in repeated follow-up or biopsy. Prostate-specific membrane antigen (PSMA) is overexpressed in hepatocellular carcinoma (HCC) neovasculature and may serve as a useful imaging biomarker. This study aimed to evaluate whether [⁶⁸Ga]Ga-PSMA-11 PET/MRI improved characterization of LR-3 observations in patients with cirrhosis compared with MRI alone. Methods: In this prospective study, conducted between March 2022 and June 2024, 19 patients with cirrhosis and 54 LR-3 observations identified on prior MRI underwent [⁶⁸Ga]Ga-PSMA-11 PET/MRI. An observation was classified as HCC if it demonstrated focal ⁶⁸Ga-PSMA uptake greater than background liver combined with at least 1 LI-RADS major or ancillary feature. The reference standard was histopathology or a follow-up MRI within 12 mo. Diagnostic metrics were calculated. Univariable logistic regression and decision tree analysis were performed to identify imaging predictors of malignancy. Results: Of the 54 LR-3 observations, 13 (24%) were confirmed as HCC and 41 (76%) as benign. [⁶⁸Ga]Ga-PSMA-11 PET/MRI correctly identified 12 of 13 HCCs (sensitivity, 92%; 95% CI, 66.7-99.6) and 39 of 41 benign observations (specificity, 95%; 95% CI, 81.9-99.3). Overall diagnostic accuracy was 94%, with a positive predictive value of 86% and negative predictive value of 97%. Diagnostic performance was significantly better than MRI alone (McNemar test, P < 0.001). [⁶⁸Ga]Ga-PSMA-11 uptake was the only significant imaging predictor of malignancy on univariable analysis (odds ratio, 5.7; P = 0.017). Decision tree analysis identified [⁶⁸Ga]Ga-PSMA-11 uptake, observation size, and hepatobiliary phase hypointensity as principal discriminators. Conclusion: [⁶⁸Ga]Ga-PSMA-11 PET/MRI demonstrates high diagnostic accuracy in differentiating malignant from benign LR-3 liver observations in patients with cirrhosis. This technique may reduce unnecessary follow-up imaging and biopsy. These results support further validation of [⁶⁸Ga]Ga-PSMA-11 PET/MRI as a promising imaging approach for indeterminate liver observations.