Prospective Comparison of 64Copper [64Cu]SAR-bisPSMA vs 68Gallium[68Ga] PSMA-11 PET/CT for Biochemical Recurrence of Prostate Cancer Following Radical Prostatectomy (Co-PSMA Trial)

Abstract

Background and objective Prostate-specific membrane-antigen positron emission tomography (PSMA-PET) has transformed management of prostate cancer biochemical recurrence (BCR) with higher diagnostic accuracy than previous imaging modalities. 64Cu-SAR-bisPSMA PET/computed tomography (CT) (64Cu-bisPSMA) is a bivalent-PSMA-peptide with 12.7-hr half-life. The study objective was detection rate (per-patient) comparison between 64Cu-bisPSMA and 68GaPSMA-11 PET/CT (68Ga-PSMA) in BCR post radical prostatectomy (RP) (NCT06907641). Methods This prospective imaging trial enrolled 50 participants with BCR (PSA 0.2–0.75 ng/ml). 64Cu-bisPSMA (1 and 24 hr) and 68Ga-PSMA were acquired within 3-wk. Images were prospectively reported, and triple read for concordance. Management impact was evaluated after 68Ga-PSMA and 64Cu-bisPSMA. A reference standard (RS) for accuracy included biopsy, targeted treatment response (no androgen deprivation therapy), PSA increase/decrease on observation or repeat imaging (64Cu-bisPSMA). The primary endpoint was mean per-participant lesional difference. Paired t tests and mixed-effects Poisson regression assessed lesion number differences between scans. Key findings and limitations Median prostate specific antigen (PSA) was 0.43 (interquartile range: 0.31–0.63). Mean per-participant lesions were higher in 64Cu-bisPSMA (1.26) versus 68GaPSMA (0.48), difference 0.78 (95% CI: 0.52–1.04), ratio 2.63 (95% CI: 1.64–4.20) ( p < 0.0001). At a per-participant level 78% (39/50) were positive on 24-hr 64Cu-bisPSMA compared to 36% (18/50) on 68GaPSMA. Management changed between scans in 22/50 (44%). 64Cu-bisPSMA were triple concordant in 84% (42/50) and 68Ga-PSMA reads in 80% (40/50). RS-true positive was 71% (24/34) versus 29% (10/34) and RS-false negative rate was 21% (7/34) versus 65% (22/34) for 64Cu-bisPSMA versus 68Ga-PSMA, respectively. Conclusion and clinical implications 64Cu-bisPSMA-PET/CT identifies a higher number of disease recurrences than 68Ga PSMA-PET/CT with substantial management impact and a high RS true positive rate in men with BCR post RP.