First-in-human Study of a Dual-modality Prostate-specific Membrane Antigen-targeted Probe for Preoperative Positron Emission Tomography/Computed Tomography Imaging and Intraoperative Fluorescence Imaging in Prostate Cancer.

Background And Objective: Accurately distinguishing between cancerous and noncancerous tissues during robot-assisted radical prostatectomy (RARP) is a challenge that can increase the risk of residual disease. This study aimed to evaluate the safety, optimal dose and accuracy of a dual-modality prostate-specific membrane antigen (PSMA)-targeted probe (Ga-P3) for preoperative positron emission tomography (PET)/computed tomography (CT) imaging and intraoperative fluorescence imaging in prostate cancer.

Methods And Surgical Procedure: Each participant received an intravenous chemical dose of Ga-P3 (10, 20, and 40 μg/kg), with radioactivity of 3.7 MBq/kg. PET/CT imaging was conducted 30, 60, and 120 min after injection to evaluate its biodistribution and dosimetry. RARP was performed at 24 ± 6 h after injection, in the sensitive mode of Firefly fluorescence imaging.

Key Findings And Limitations: Between May 2024 and July 2024, a total of 16 patients were included; Ga-P3 was well tolerated without any adverse events related to Ga-P3 administration or fluorescence imaging. At 2 h after administration, the median tumor maximum standardized uptake value was 5.3 (4.1-8.1). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Ga-P3 PET/CT for tumor localization were 79.1%, 90.4%, 81.5%, and 89.0%, respectively. The overall NPV, PPV, and accuracy of intraoperative fluorescence imaging were 100%, 43.8%, and 90.9%, respectively. Of overall false-positive sites, 88.9% (8/9) were confirmed as tumor adjacent to the surgical margin. A dose of 40 μg/kg resulted in the highest accuracy of 92.3%.

Conclusions And Clinical Implications: In PSMA-targeted PET imaging and fluorescence-guided surgery, Ga-P3 is safe and feasible for use, offering a novel tool for the surgical management of prostate cancer.