⁶¹ Cu-NODAGA Prostate-specific Membrane Antigen Imaging and Therapy for Prostate Cancer: Phase 1 Trial of a New Class of ⁶¹ Cu-labeled PET Radiotracers

Background Prostate-specific membrane antigen (PSMA)-targeted PET has revolutionized prostate cancer imaging, but the sensitivity at low prostate-specific antigen levels is lacking. Copper 61 (⁶¹Cu) is a positron emitter with favorable physical characteristics that allow for delayed imaging, which may result in improved sensitivity. Purpose To evaluate the safety, dosimetry, optimal imaging parameters, and initial efficacy of a novel ⁶¹Cu-labeled PSMA-targeting radiotracer, ⁶¹Cu-1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA)-PSMA for imaging and therapy (I&T) (hereafter, ⁶¹Cu-PSMA I&T). Materials and Methods This was a phase 1 trial of the ⁶¹Cu-labeled PSMA-targeting radiotracer, ⁶¹Cu-PSMA I&T (NCT06736054). Between October 2024 and February 2025, participants with PSMA-avid disease at fluorine 18 (¹⁸F)-piflufolastat PET/CT performed within 30 days of ⁶¹Cu-PSMA I&T PET/CT were administered 155-318 MBq of ⁶¹Cu-PSMA and then underwent PET/CT 1, 2, and 4 hours after administration and blood sampling for dosimetry. The number of suspected malignant lesions and the degree of radiotracer uptake in lesion and background tissues were compared between ⁶¹Cu-PSMA I&T and ¹⁸F-piflufolastat. Results Eight male participants (mean age, 73 years ± 10.9 [SD]) completed the trial. No adverse events were noted. A low dose of 155 MBq of ⁶¹Cu-PSMA I&T was adequate for imaging. Dosimetry calculations demonstrated that the kidney (mean, 0.30 mGy/MBq) and lacrimal glands (mean, 0.17 mGy/MBq) received the highest doses, whereas the whole-body mean effective dose was 0.029 mSv/MBq. ⁶¹Cu-PSMA I&T PET/CT images obtained 4 hours after tracer administration showed the largest number of suspected malignant lesions, the highest radiotracer uptake in the lesions, and the lowest radiotracer uptake in the background tissues. In four of the eight participants, more suspected malignant lesions were identified with ⁶¹Cu-PSMA I&T than with ¹⁸F-piflufolastat. Conclusion ⁶¹Cu-PSMA I&T was well tolerated, and no adverse events were reported in this phase 1 trial. ⁶¹Cu-PSMA I&T demonstrated acceptable dosimetry and was used for successful imaging in patients with metastatic prostate cancer. Optimal images were obtained 4 hours after tracer administration. ClinicalTrials.gov identifier no. NCT06736054. © RSNA, 2025 <i>Supplemental material is available for this article.</i> See also the editorial by Sinha and El Khouli in this issue.