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

Abstract

32 Background: PET-based radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have become the mainstay of prostate cancer imaging; however, high urinary radioactivity from these primarily renally cleared compounds may obscure tumors in the prostate and peri-ureteric regions. We conducted the first intra-patient comparator study to assess the urinary radioactivity of two 18 F-labelled PSMA-PET radiopharmaceuticals, 18 F-piflufolastat and 18 F-flotufolastat. Methods: This multicenter, prospective, intra-patient comparator study (NCT06604442) enrolled men ≥ 18 years with low PSA (≤ 0.5 ng/mL) biochemical recurrence of prostate cancer ≥ 6 months after radical prostatectomy with undetectable PSA post-surgery, scheduled for a standard-of-care (SoC) 18 F-piflufolastat PET. Patients had a SoC PET/CT after IV 18 F-piflufolastat (target dose 333 MBq), and a second PET/CT 1–10 days later after IV 18 F-flotufolastat (target dose 296 MBq), both scans started approximately 60 min after administration and used the same scanner. The primary endpoint was the difference in urinary bladder radioactivity (mean standardized uptake value [SUV mean ]) between 18 F-piflufolastat PET and 18 F-flotufolastat PET. Secondary endpoints included patient and region-level detection rates (DR) for each radiopharmaceutical. Images were interpreted by two blinded central readers, with a third to resolve disagreements, allowing majority read results. Results: Between Oct 2024 and Jun 2025, 55 patients (mean PSA, 0.28 [range 0.09–0.50] ng/mL) were included in the primary efficacy analysis. Median bladder SUV mean was significantly higher with 18 F-piflufolastat (29.0; interquartile range [IQR], 18.9–40.8) than 18 F-flotufolastat (10.9; IQR, 6.0–18.5) with a median difference of 15.1 (IQR, 8.5–27.0; p<0.001 [Wilcoxon signed-rank test]). The patient-level DR was 27.3% (15/55) for 18 F-piflufolastat and 45.5% (25/55) for 18 F-flotufolastat (majority read). Among the 21 patients with very low PSA levels (≤ 0.2 ng/mL), 38.1% had a positive 18 F-piflufolastat scan compared with 52.4% for 18 F-flotufolastat scans (majority read). Regional and sub-regional DRs are shown in the table. Conclusions: In this intra-patient study, 18 F-flotufolastat showed significantly lower urinary radioactivity, and a higher overall DR than 18 F-piflufolastat indicating it may offer improved image assessment in regions close to the bladder. Clinical trial information: NCT06604442 . Region 18 F-Piflufolastat DR* n (%)N=55 18 F-Flotufolastat DR*n (%)N=55 Prostate bed 6 (10.9) 10 (18.2) Vesicourethral anastomosis 1 (1.8) 4 (7.3) Retrovesical 2 (3.6) 2 (3.6) Remnant seminal vesicles/ lateral surgical margin 2 (3.6) 4 (7.3) Pelvic lymph nodes 8 (14.5) 9 (16.4) Majority read. *≥ 1 PET positive lesion.