Diuresis During F-Flotufolastat (rhPSMA-7.3) PET/CT Improves Recurrence Detection After Prostatectomy: A Prospective Phase II Trial.

Radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have emerged as a sensitive tool for PET imaging of prostate cancer (PCa) recurrence. Yet urinary bladder activity may obscure the visualization of prostate bed recurrence. Among the Food and Drug Administration-approved PSMA radiopharmaceuticals, F-flotufolastat (rhPSMA-7.3) has the lowest urinary excreted activity. We investigated the impact of diuresis with intravenous furosemide and oral hydration on bladder activity and PCa recurrence detection in patients with PCa after prostatectomy with biochemical recurrence. This phase II study (NCT05779943) prospectively recruited men with PCa after prostatectomy with a rising prostate-specific antigen (PSA) level of at least 0.1 ng/mL. All patients had 2 F-flotufolastat PET/CT scans, one with 20 mg of furosemide administered intravenously with the radiotracer and the other without. SUV, SUV, and bladder volume were compared between the with- and without-furosemide PET/CT studies. PCa lesion detection was compared between the 2 sets of scans. Twenty men with a median PSA of 0.61 ng/mL (interquartile range, 0.18-1.15) completed both sets of scans. Bladder activity was significantly lower for the with- than the without-furosemide studies, at a median SUV of 4.20 (range, 1.70-19.80) versus 13.35 (range, 3.90-165.4), respectively ( = 0.014), and a median SUV of 2.95 (range, 0.80-17.60) versus 10.00 (range, 1.90-140.00), respectively ( = 0.017). Multivariable analysis demonstrated that both furosemide administration and bladder distention were independent covariates for reduced bladder activity. At the prostate bed region level, the recurrence detection rates were 17 of 20 (85%) and 12 of 20 (60%) for the with- and without-furosemide studies, respectively ( = 0.025). No difference in detection rates was present at the per-patient, pelvic, or extrapelvic regions between the 2 sets of studies. Three of 20 without-furosemide studies had a mild noninterfering peribladder halo artifact, but none had an artifact with furosemide. In men with biochemical recurrence and a PSA level of at least 0.1 ng/mL after prostatectomy for PCa, a strategy with F-flotufolastat PET/CT and concordant low-dose furosemide further reduces urinary bladder intensity and increases local recurrence detection. Even without the use of a diuretic, relative bladder distension alone also reduces bladder activity, though not to the same degree as with a diuretic.