Optimization of Administered Activity for 64Cu-SAR-bisPSMA PET Imaging in Primary Prostate Cancer: Results from a Phase I Retrospective Study (PROPELLER Sub-study)

Abstract

68Ga- and 18F-labeled prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) agents have advanced prostate cancer (PC) imaging. 64Cu-SAR-bisPSMA may offer several advantages for imaging of PC over standard-of-care PSMA PET agents due to its sarcophagine chelator, bivalent structure and longer half-life of 64Cu (12.7h vs. <2h for 68Ga and 18F), which may lead to detection of additional and smaller lesions. This study determined the administered activity (AA) of 64Cu-SAR-bisPSMA required to achieve diagnostic-quality imaging for clinical use.

The PROPELLER trial (CLP03; NCT04839367) enrolled 30 men with untreated, histopathology-confirmed, primary PC with intermediate- to high-risk features. Participants received an intravenous injection of 64Cu-SAR-bisPSMA at 100, 150, or 200 MBq, followed by whole-body PET/computed tomography 2 to 4 hours post-injection. Images were anonymized, randomized, and reviewed by two blinded central readers using the three-point Image Utility Classification Score. For intra-individual comparisons, a subset of images acquired at 200 MBq were digitally reconstructed to simulate 100 and 150 MBq acquisitions on the same scanner; these were randomized and then evaluated by a blinded reader. They were ranked from best image to worst image and scored with a 4-item, 5-point Likert Image Quality Score (maximum 20 points). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also measured.

Mean Image Utility Classification Score was the highest in the 200 MBq 64Cu-SAR-bisPSMA cohort compared with the 100 and 150 MBq cohorts (1.44, 1.17, and 0.92, respectively). For the intra-individual comparisons, images corresponding to 200 MBq were ranked as having the best image quality with a statistically significant difference in image quality ranking between AAs (p = 0.0025). The mean Image Quality Score was highest at 200 MBq of 64Cu-SAR-bisPSMA (16.0 ± standard deviation 1.10) versus 150 MBq (12.2 ± 1.17) and 100 MBq (10.3 ± 1.63). Quantitatively, 200 MBq of 64Cu-SAR-bisPSMA had the greatest SNR in both the liver and prostate and the highest CNR for liver relative to the gluteus muscle.

An AA of 200 MBq was identified as the optimal AA for 64Cu-SAR-bisPSMA PET, yielding improved image quality across both qualitative and quantitative metrics compared with 150 and 100 MBq. These findings support the selection of 200 MBq for clinical studies evaluating 64Cu-SAR-bisPSMA as an imaging agent for PC. NCT04839367, Registered 2021–04–07.