Abstract
Purpose This prospective, multicentre, intra-patient comparator study assessed urinary radioactivity, and patient-level and region-level detection rates (DR) with PSMA-PET radiopharmaceuticals, F-18-piflufolastat (F-18-DCFPyL) and F-18-flotufolastat (F-18-rhPSMA-7.3) in patients with biochemical recurrence (BCR) of prostate cancer to evaluate the hypothesis that lower urinary radioactivity is observed with F-18-flotufolastat. Methods Patients with low PSA (<= 0.5 ng/mL) BCR >= 6 months post-prostatectomy with undetectable PSA post-surgery, scheduled for standard-of-care F-18-piflufolastat PSMA-PET were enrolled. Patients underwent PET/CT 60 minutes post-F-18-piflufolastat (9 mCi) administration, and a second PET/CT on the same scanner 1-10 days later, 60 minutes post-F-18-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). Results Fifty-five evaluable patients (mean PSA, 0.28 ng/mL) were enrolled. Median bladder SUVmean was significantly higher with F-18-piflufolastat (29.0; interquartile range, 18.9-40.8) than F-18-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 F-18-piflufolastat and 45.5% (25/55) for F-18-flotufolastat. Region-level DR for F-18-piflufolastat and F-18-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 F-18-piflufolastat and F-18-flotufolastat scans, respectively. Conclusions This intra-patient comparator shows F-18-flotufolastat has significantly lower urinary radioactivity than F-18-piflufolastat, which may help to optimise image assessment in regions close to the urinary tract.