Diagnostic Performance of [18F]PSMA-1007 PET/CT on Proven PSMA-Positive Hepatocellular Carcinoma: A Prospective Clinical Study.

High expression of prostate-specific membrane antigen (PSMA) is not limited to prostate cancer but can be found in other tumor entities, such as hepatocellular carcinoma (HCC), and could possibly be used for theranostic purposes. Our aim was to investigate the diagnostic potential of the hepatobiliary excreted radiotracer [18F]PSMA-1007 on initial staging of HCC. Methods: This prospective clinical study (NCT05547919) included 10 participants (9 men, 1 woman) with treatment-naïve, histopathologically proven PSMA-positive HCC. All participants underwent [18F]PSMA-1007 PET with unenhanced low-dose CT. All scans were analyzed visually and quantitatively. We assessed the SUVmax of the primary tumor and the SUVmean of nonaffected liver parenchyma and calculated tumor-to-background ratios (i.e., SUVmax HCC/SUVmean liver) for each patient. In addition, we assessed possible eligibility for PSMA-directed radiopharmaceutical therapy according to the PROMISE criteria. The presence of local lymph nodes and distant metastases was noted for [18F]PSMA-1007 PET/CT and compared with the results of contrast-enhanced CT of the trunk and MRI of the upper abdomen. Possible prognostic implications of PSMA expression on immunohistochemistry and on [18F]PSMA-1007 PET/CT were compared with progression-free survival (defined as clinical progression, radiographic progression, or death from any cause) using Cox regression. Results: [18F]PSMA-1007 PET showed high uptake in 7 of 10 patients (PROMISE score 2, n = 4; PROMISE score 3, n = 3); mediocre or missing uptake was found in 3 participants (PROMISE score 0, n = 1; PROMISE score 1, n = 2). The median tumor-to-background ratio was 2.7 (interquartile range, 2.65). [18F]PSMA-1007 PET did not reveal new distant metastatic lesions compared with contrast-enhanced CT. In 1 patient, local lymph node metastases were considered PSMA-negative despite high uptake in the primary tumor. Whether assessed ex vivo or in vivo, PSMA expression did not correlate with progression-free survival. Conclusion: [18F]PSMA-1007 can be used depict untreated HCC and shows high uptake relative to background, indicative of excellent image contrast. High tracer accumulation in 70% of the participants suggests a possible use for PSMA-directed radiopharmaceutical therapy in an end-stage setting. However, PSMA expression was not prognostic for outcome, possibly because of the small sample size.