Radiology. 2025 Dec;317(3):e251151. doi: 10.1148/radiol.251151.
ABSTRACT
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 Supplemental material is available for this article. See also the editorial by Sinha and El Khouli in this issue.
PMID:41363974 | DOI:10.1148/radiol.251151
