Pharmacokinetic Comparison of Selective Prostatic Arterial and Intravenous PSMA PET/CT Radioligand Infusions in Primary Prostatic Adenocarcinoma

Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (⁶⁸Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic ⁶⁸Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUV_max) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUV_mean) in prostatic tumoral VOIs and area under the SUV_mean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUV_max and SUV_mean time-activity curves (TACs), and paired <i>t</i> tests were used for the remaining data. Results The mean SUV_max within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (<i>P</i> = .008). The SUV_mean within VOIs was greater during arterial sessions (<i>P</i> < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (<i>P</i> = .002). Conclusion Selective prostatic arterial infusion resulted in greater ⁶⁸Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 <i>Supplemental material is available for this article.</i> See also the editorial by Civelek in this issue.