First-in-human study of DGPR1008 for intraoperative fluorescence imaging of prostate-specific membrane antigen-positive prostate cancer in patients undergoing radical prostatectomy

Background: Prostate cancer (PCa) precise surgical resection remains a critical challenge due to positive margins compromising outcomes. This study sought to explore the safety and efficacy of DGPR1008, a novel near-infrared (NIR) prostate-specific membrane antigen (PSMA)-targeted fluorescent contrast agent, in fluorescence-guided surgery (FGS) of PCa. Methods: This single-center, open-label, prospective, single-arm, exploratory study was carried out in The Fourth Affiliated Hospital of Soochow University, China. Patients newly diagnosed with PCa (a Gleason score ≥7) were eligible for enrollment. All patients underwent laparoscopic radical prostatectomy (LRP) with pelvic lymph node dissection (PLND) using DGPR1008. Four dose cohorts were studied: dose cohort A, which received 0.06 mg/kg of DGPR1008 24 h preoperatively; dose cohort B, which received 0.03 mg/kg of DGPR1008 24 h preoperatively; dose cohort C, which received 0.03 mg/kg of DGPR1008 12 h preoperatively, and dose cohort D, which received 0.045 mg/kg of DGPR1008 24 h preoperatively. Safety and efficacy were assessed. Results: From July, 2023 to January, 2024, 14 eligible patients were included in the study. In total, 32 adverse events (AEs) were observed. One patient (7.1%) presented with four serious adverse events (SAEs), including urinary fistula, infected lymphocele, wound complications, and acute exacerbation of chronic obstructive pulmonary disease. None of the AEs or SAEs was found to be associated with the administration of DGPR1008. Compared with the other dose cohorts, DGPR1008 showed the highest sensitivity (80.6%) for detecting PCa in vivo in dose cohort B. Further, dose cohort B provided the highest target-to-background ratio (TBR) through all phases of tumor imaging, both in vivo and ex vivo, on the gross and fixed tissue. DGPR1008 enabled the real-time visualization of tumor-positive surgical margins, and had a sensitivity of 90% in vivo and 100% ex vivo. Conclusions: DGPR1008 is safe and well tolerated, and may be used in the intraoperative identification of primary PCa and positive surgical margins. Dose cohort B (0.03 mg/kg, 24 h preoperatively) is optimal for efficacy and TBR.