An intra-patient contemporaneous comparison of 18F-piflufolastat and 18F-flotufolastat urinary radioactivity and pelvic region detection rates in men with low PSA biochemical recurrence of prostate cancer after radical prostatectomy

This prospective, multicentre, intra-patient comparator study assessed urinary radioactivity, and patient-level and region-level detection rates (DR) with PSMA-PET radiopharmaceuticals, 18F-piflufolastat (18F-DCFPyL) and 18F-flotufolastat (18F-rhPSMA-7.3) in patients with biochemical recurrence (BCR) of prostate cancer to evaluate the hypothesis that lower urinary radioactivity is observed with 18F-flotufolastat. Patients with low PSA (≤0.5 ng/mL) BCR ≥6 months post-prostatectomy with undetectable PSA post-surgery, scheduled for standard-of-care 18F-piflufolastat PSMA-PET were enrolled. Patients underwent PET/CT 60 minutes post-18F-piflufolastat (9 mCi) administration, and a second PET/CT on the same scanner 1–10 days later, 60 minutes post-18F-flotufolastat (8 mCi) administration. The primary endpoint was the difference in urinary radioactivity (SUVmean) between the radiopharmaceuticals. Secondary endpoints included patient-level and region-level DR for each radiopharmaceutical, assessed by two blinded readers (a third resolved disagreements, allowing majority reads). Fifty-five evaluable patients (mean PSA, 0.28 ng/mL) were enrolled. Median bladder SUVmean was significantly higher with 18F-piflufolastat (29.0; interquartile range, 18.9–40.8) than 18F-flotufolastat (10.9; interquartile range, 6.0–18.5; p < 0.001 [Wilcoxon signed-rank test]). Majority read patient-level DR were 27.3% (15/55) for 18F-piflufolastat and 45.5% (25/55) for 18F-flotufolastat. Region-level DR for 18F-piflufolastat and 18F-flotufolastat, were 10.9% (6/55) and 18.2% (10/55) in the prostate bed, 14.5% (8/55) and 16.4% (9/55) in pelvic lymph nodes, and 7.3% (4/55) and 21.8% (12/55) in extra-pelvic sites. Among patients with PSA ≤0.2 ng/mL, 38.1% (8/21) and 52.4% (11/21) had positive 18F-piflufolastat and 18F-flotufolastat scans, respectively. This intra-patient comparator shows 18F-flotufolastat has significantly lower urinary radioactivity than 18F-piflufolastat, which may help to optimise image assessment in regions close to the urinary tract. Trial registration, clinicaltrials.gov: NCT06604442. Registered September 2024.