Abstract B054: Phase 1 study of 61Cu-NU101 in patients with prostate cancer

Abstract Background: Prostate Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionized prostate cancer imaging, but sensitivity at low PSA levels is still problematic, and delivery of these agents is limited due to the short half-life of many PET radioisotopes. 61Cu is a positron emitter with favorable physical characteristics, which allows for delivery of agents over long distances and delayed imaging which may improve sensitivity. This phase 1 trial was designed to evaluate the safety, dosimetry, optimal imaging parameters, and initial efficacy of a 61Cu-labelled PSMA-targeting radiotracer, 61Cu-NODAGA-PSMA I&T (61Cu-PSMA). Methods: A phase 1 trial of a 61Cu-labelled PSMA-targeting radiotracer, 61Cu-NODAGA-PSMA I&T (61Cu-PSMA) was performed (NCT06736054). Subjects with PSMA-avid disease on a 18F-Piflufolastat PET/CT within 30 days underwent administration of 4.2-8.6 mCi of 61Cu-PSMA, PET/CT imaging at 1, 2, and 4 hours post administration, and blood sampling for dosimetry. Number of suspected malignant lesions and radiotracer uptake in lesional and background tissues were compared between 61Cu-PSMA and 18F-Piflufolastat. Results: Eight subjects completed the trial. 4-hour delayed 61Cu-PSMA PET/CT images demonstrated the most suspected malignant lesions, the highest radiotracer uptake in lesions, and the lowest radiotracer uptake in background tissues. In 4 of 8 participants, more suspected malignant lesions were identified with 61Cu-PSMA than with 18F-Piflufolastat. Dosimetry calculations were comparable to other PSMA-targeted tracers. No adverse events were noted. Conclusion: 61Cu-PSMA was safe and effective for PSMA-targeted imaging of prostate cancer, with optimal images obtained 4 hours post tracer administration and higher sensitivity than a current leading PSMA-targeted imaging agent. This supports development of 61Cu-PSMA as a novel PSMA-targeting imaging agent. More broadly, the success of this first 61Cu PET radiotracer opens new opportunities for the construction of novel 61Cu PET radiotracers for multiple malignancies. The favorable physical characteristics of 61Cu allow development of new radiopharmaceuticals with high sensitivity. Citation Format: Ben Pais, Jeffrey C. Bassett, Ryan Reddy, Beth Thomson, Danett Reynolds, KJ Jerjian, Ryan Wolfe, David J. Benjamin, Melpomeni Fani, Joe O'Donoghue, Markus Baier, Nicole Schubert, Francesco De Rose, Leila Jaafar. Phase 1 study of 61Cu-NU101 in patients with prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B054.