Intra-patient comparison of urinary radioactivity after
18
F-piflufolastat and
18
F-flotufolastat PET in men with low PSA biochemical recurrence of prostate cancer who have had radical prostatectomy.
Authors: Andrews Jack , Josephson David , Saltzstein Daniel R. , Purysko Andrei , Shore Neal D. , Gartrell Benjamin , Pathak Ram , Kuo Phillip H. , Sykes James , Davis Phillip , Helfand Brian T. 
Published: February 2025

TPS272

Background:
Prostate-specific membrane antigen (PSMA)-targeting positron emission tomography (PET) radiopharmaceuticals enable early detection of metastatic and recurrent prostate cancer (PCa). High urinary radioactivity of some PSMA-PET agents can affect interpretation of scans in the pelvic region (prostate/prostate bed [PB]; pelvic lymph nodes [PLN]).
18
F-Piflufolastat and
18
F-flotufolastat are FDA-approved, mainly renally cleared, diagnostic PSMA-PET agents; data suggest
18
F-flotufolastat has lower urinary radioactivity than
18
F-piflufolastat, but no clinical differences have been confirmed by head-to-head intra-patient studies. The present study will directly compare the urinary radioactivity of
18
F-piflufolastat with
18
F-flotufolastat in men with low prostate-specific antigen (PSA) biochemical recurrence (BCR) of PCa after radical prostatectomy (RP).
Methods:
This multicenter, prospective, intra-patient comparator study will include men (≥ 18 years old) with low PSA (≤ 0.5 ng/mL) BCR of PCa who have had RP ≥ 6 months before enrollment (with undetectable PSA post surgery) and are due to have routine
18
F-piflufolastat PET. Men who have had prior
18
F-piflufolastat PET or salvage therapy, or with conditions affecting urinary output, will be excluded. Eligible patients will undergo
18
F-piflufolastat PET followed by
18
F-flotufolastat PET ≥ 24 hours but ≤ 10 days later. No diuretic will be administered for scanning purposes. Each radiopharmaceutical will be administered as a single intravenous bolus per approved US prescribing information (USPI). Scanning (with the same scanner for both scans) will start 50–90 minutes post injection of
18
F-piflufolastat and 50–70 minutes post injection of
18
F-flotufolastat. Each patient will be their own control. The primary endpoint will be difference in mean standardized uptake value (SUV
mean
) between
18
F-piflufolastat and
18
F-flotufolastat as assessed in volumes of interest drawn on the urinary bladder. Secondary endpoints for both agents will include detection rates: at the patient level (overall; by baseline PSA); for local recurrences in PB subregions; and for PLN lesions. For secondary endpoints, PET scans will be interpreted per product-specific USPI by 2 specially trained, blinded, central readers (a third reader will adjudicate disagreements). Safety will be monitored until 24 hours after the second scan. Around 60 men will be screened and ≥ 52 with evaluable PET scans for both agents will be included in the primary analysis. The primary endpoint will be assessed for normality and a difference in SUV
mean
will be tested using 2-sided paired tests (Wilcoxon signed-rank test [non-normal]; t-test [normal]). All further endpoints, including safety, will be summarized descriptively. The trial has been open for enrollment since 10/24. Clinical trial information:
NCT06604442
.