COBRA Study Highlights Efficacy of 64Cu-SAR-bisPSMA for Detecting Recurrent Prostate Cancer

The phase 1/2 COBRA trial evaluated the novel radiotracer ⁶⁴Cu-SAR-bisPSMA in detecting biochemical recurrence (BCR) of prostate cancer (PC). The study, presented at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting by lead author Luke Nordquist, MD, FACP, CEO of the Urology Cancer Center in Omaha, Nebraska, focuses on patients with rising prostate-specific antigen (PSA) levels postdefinitive therapy who had negative or inconclusive standard imaging results.

Prostate-specific membrane antigen (PSMA) is a key target in PC imaging due to its high expression in PC cells. ⁶⁴Cu-SAR-bisPSMA, with its bivalent structure and longer half-life (12.7 hours), shows promise over existing PSMA positron emission tomography (PET) agents like ¹⁸F and ⁶⁸Ga. This study aimed to determine the safety and effectiveness of ⁶⁴Cu-SAR-bisPSMA in detecting recurrent PC.

The COBRA trial involved 52 patients, of whom 32 completed the study. Eligible participants had adenocarcinoma of the prostate, rising PSA levels, and negative or equivocal findings on standard imaging methods, including PSMA PET, computed tomography (CT), or bone scan. Patients received a single dose of ⁶⁴Cu-SAR-bisPSMA (200 MBq) and underwent PET/CT scans on the same day (day 0) and the following day (day 1). Primary objectives were safety and detection rates, while secondary end points included standardized uptake values (SUVs) and tumor-to-background ratios (TBRs).

The trial reported no significant changes in laboratory values and only 1 treatment-related adverse event (grade 2 worsening of type 2 diabetes, which resolved). Detection rates (DRs) on day 0 ranged from 44% to 58%, increasing to 58% to 80% on day 1, indicating more effective detection with delayed imaging. Correct DRs also improved from same-day to next-day imaging, with additional lesions found in all anatomical regions on day 1.

The true negative rates (TNRs) remained high across both days, showing consistent reliability in excluding false positives. For instance, TNRs in the pelvic region ranged from 93.8% to 96.9% on day 0 and from 81.3% to 87.9% on day 1. Similarly, TNRs for extrapelvic regions ranged from 93.9% to 97.0% on day 0 and from 90.9% to 97.0% on day 1.

Quantitative assessments showed higher SUVmean, SUVmax, and TBRs on day 1 compared with day 0, further supporting the efficacy of delayed imaging in identifying cancerous lesions.

The COBRA study demonstrates that ⁶⁴Cu-SAR-bisPSMA is both safe and effective for detecting PSMA-expressing PC, especially in cases where standard imaging fails to provide clear results. The study highlights the improved detection capabilities of ⁶⁴Cu-SAR-bisPSMA on delayed (next-day) imaging, identifying more lesions and providing higher SUVs and TBRs compared with same-day imaging.