Molecular Imaging in Focus: Can the Emerging PET Agent 64Cu-SAR-bisPSMA Improve Detection for Biochemical Recurrence of PCa?

One of the challenges with currently approved PSMA PET agents is questionable reliability for detecting biochemical recurrence (BCR) of prostate cancer (PCa) in patients with low prostate-specific antigen (PSA) levels.

“One of the problems we have with all the approved PSMA pet agents at the moment is at very low PSA levels. So (in) men with PSA below 0.5 ng/mL who have biochemical recurrence following radical prostatectomy, the detection rate is only about 30 to 50 percent in just about all studies. So we cannot identify biochemical recurrence in these men at levels at which they're still curable with salvage radiotherapy. That is a key unmet need with PSMA PET in the prostate cancer space,” maintained Louise Emmett, MBChB, FRACP, FAANMS, MD, in a recent interview with Diagnostic Imaging.

Accordingly, researchers in the recent phase 2 Co-PSMA trial compared the emerging PET agent ⁶⁴Cu-SAR-bisPSMA (Clarity Pharmaceuticals) to ⁶⁸Ga-PSMA-11 in 50 patients with low PSA levels (ranging between 0.2-0.75 ng/mL) and biochemical recurrence of PCa.

After the use of ⁶⁸Ga-PSMA-11, the study authors found that subsequent PET imaging with ⁶⁴Cu-SAR-bisPSMA detected more than double the number of PCa lesions (63 vs. 24) and more than double the number of positive PET scans (78 percent vs. 36 percent).

(Editor’s note: For related content on prostate cancer imaging, click here.)

Dr. Emmett, the primary investigator for the Co-PSMA trial, cited the increased binding and the longer half-life (12 hours) of ⁶⁴Cu-SAR-bisPSMA as being particularly advantageous for detecting PCa BCR.

“It's the double whammy, I think, of the bifid structure and the long half-life of the PET agent, which gives more time for it to concentrate in the cancer and then wash out of all the other structures. That makes it really nice, particularly in this biochemical recurrence setting,” noted Dr. Emmett, the director of theranostics and nuclear medicine at St. Vincent’s Hospital Sydney in Sydney, Australia.

While cautioning that further research with larger cohorts is needed to validate the findings from the Co-PSMA study, Dr. Emmett said she is “thrilled” with the 78 percent detection rate for PCa BCR with ⁶⁴Cu-SAR-bisPSMA and the potential implications for treatment.

“One of the things I really liked about the trial is that the active management of these patients went from 66 percent with the gallium(-based PET agent) up to 90 percent after they had the copper-based PSMA scans. Perhaps they're being treated more appropriately. I can't say that exactly, but we know all these patients have recurrent disease. We know they had a good response to treatment, and I think that's a great start,” emphasized Dr. Emmett, a conjoint professor with the faculty of medicine at the University of South Wales in Sydney, Australia.

(Editor’s note: For related content, see “The Reading Room Podcast: Current Insights and Emerging Trends in Molecular Imaging and Theranostics for Prostate Cancer,” “Comparative PET Imaging Trial Shows Increased Detection of PCa Recurrence with 64Cu-SAR-bisPSMA” and “Molecular Imaging in Focus: Emerging Insights on the PET and SPECT Imaging Agent 61Cu-NU101 for PCa.”)