Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis.

Purpose: Actinium-225 labeled prostate-specific membrane antigen (PSMA) targeted radionuclide therapy has emerged as a potential treatment option in the management of men with metastatic castrate-resistant prostate cancer (mCRPC). This study investigated molecular imaging-derived parameters and compared imaging response of lesions categorized by tumor site.

Methods: Men with mCRPC treated with [225Ac]Ac-J591 from 2017 to 2022 at our center on two prospective trials (NCT03276572 and NCT04506567) with pre- and post-treatment [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET) imaging studies available were included. SUVpeak of the 3 most- and 3 least-avid lesions of the tumor sites were manually assessed. The median change of the SUVpeak from pre- to post-treatment per tumor site was evaluated using the paired Wilcox test. An objective response (OR) in the follow-up image was defined as complete or partial response using PET Response Criteria in Solid Tumors (PERCIST) 1.0.

Results: A total of 46 cases met the criteria for image review; most of them (n = 25, 54.3%) had more than one tumor site category. In total, 445 PSMA PET-positive lesions were assessed: 220 osseous, 163 nodal, 41 visceral, and 21 prostatic lesions. After treatment with [225Ac]Ac-J591, absolute SUVpeak values per tumor site declined significantly (p < 0.05) except for prostatic lesions (p = 1). The PERCIST-OR rate for osseous, nodal, visceral, and prostatic lesions was 53%, 28%, 56%, and 38%, respectively.

Conclusion: [225Ac]Ac-J591 is an active treatment in men with mCRPC. Tumor distribution patterns may influence treatment response and potentially prognosis. Our findings warrant further validation in a larger cohort but may be considered in treatment planning and trial design.