Prostate-specific membrane antigen (PSMA) PET imaging plays a central role in evaluating biochemical recurrence after radical prostatectomy. Yet, high urinary radioactivity from renally cleared 18F-labeled tracers may obscure lesions near the bladder and prostate bed. This is an especially important limitation in men with very low prostate-specific antigen (PSA) levels. In a prospective intra-patient comparator study, investigators assessed urinary radioactivity and detection rates with 18F-piflufolastat versus 18F-flotufolastat in men with low-PSA recurrence.
Clinical Takeaway
In men with low-PSA biochemical recurrence following radical prostatectomy, 18F-flotufolastat demonstrated significantly lower urinary radioactivity and higher patient-level detection rates compared with 18F-piflufolastat. Reduced bladder activity may improve assessment of disease in regions adjacent to the prostate bed, particularly in patients with very low PSA levels.
Radiotracer / Imaging Agent Profile
- Radiotracer Class: 18F-labeled PSMA PET radiopharmaceuticals
- Agents Compared: 18F-piflufolastat vs 18F-flotufolastat (Posluma)
- Clinical Use Case: PSMA PET/CT imaging in biochemical recurrence after radical prostatectomy
- Key Limitation Addressed: Urinary radioactivity obscuring lesions in the prostate bed and peri-ureteric regions
- Read Method: Two blinded central readers with third-reader adjudication (majority read)
- Clinical Role: Evaluation of suspected biochemical recurrence, particularly in regions adjacent to the bladder and prostate bed
Target Population
- Men ≥18 years
- Biochemical recurrence after radical prostatectomy
- PSA ≤0.5 ng/mL
- ≥6 months post-prostatectomy
- Undetectable PSA following surgery
- Scheduled for standard-of-care 18F-piflufolastat PET/CT
Study Design (NCT06604442)
- Study Type: Multicenter, prospective, intra-patient comparator study
- Setting: Multicenter PET/CT imaging centers
- Design: Each patient underwent PET/CT with both tracers 1–10 days apart using the same scanner, imaging initiated approximately 60 minutes post-injection
- Population: 55 men ≥ 18 years of age with low PSA (≤0.5 ng/mL) biochemical recurrence ≥6 months after radical prostatectomy
- Comparator: 18F-piflufolastat vs 18F-flotufolastat (intra-patient comparison)
Key Endpoints
- Primary Endpoint:
- Difference in urinary bladder SUVmean between 18F-piflufolastat and 18F-flotufolastat
- Key Secondary Endpoints:
- Patient-level detection rate
- Region-level detection rate (prostate bed and pelvic nodes)
Key Results
- Urinary Radioactivity (Primary Endpoint):
- Median urinary bladder SUVmean was significantly higher with 18F-piflufolastat (29.0; IQR 18.9–40.8) compared with 18F-flotufolastat (10.9; IQR 6.0–18.5), with a median difference of 15.1 (IQR 8.5–27.0; p < 0.001).
- Detection Rates (Patient-Level):
- The overall patient-level detection rate was 27.3% (15/55) with 18F-piflufolastat compared with 45.5% (25/55) with 18F-flotufolastat (majority read).
- Among patients with very low PSA levels (≤0.2 ng/mL), detection rates were 38.1% with 18F-piflufolastat versus 52.4% with 18F-flotufolastat.
- Regional Detection Rates:
- Regional detection differences were most pronounced in prostate bed subregions.
- Prostate bed: 10.9% vs 18.2%
- Vesicourethral anastomosis: 1.8% vs 7.3%
- Pelvic nodes: 14.5% vs 16.4%
- Regional detection differences were most pronounced in prostate bed subregions.
Key Clinical Implications
✔ Lower urinary activity may enhance visualization of lesions adjacent to the bladder and prostate bed
✔ Higher detection rates suggest potential sensitivity advantages in low-PSA recurrence
✔ Intra-patient design reduces inter-patient variability and strengthens comparative validity
✔ Findings require validation beyond abstract data and correlation with downstream clinical outcomes
Bottom Line
In this prospective intra-patient comparator study, 18F-flotufolastat demonstrated lower urinary bladder radioactivity and higher lesion detection rates compared with 18F-piflufolastat in men with early biochemical recurrence. While longer-term outcome correlation is needed, reduced bladder activity may represent a meaningful imaging advantage in early recurrence settings.
Sources:
- Blue Earth Diagnostics. Blue Earth Diagnostics announces positive head-to-head comparator study results for POSLUMA® (flotufolastat F 18) versus piflufolastat F 18 in men with low PSA biochemical recurrence after radical prostatectomy. Published February 2026. Accessed March 3, 2026. https://www.blueearthdiagnostics.com/hubfs/Comparator%20Study%20Results%20Press%20Release_Final.pdf
- ClinicalTrials.gov. An intra-patient comparator study of 18F-piflufolastat and 18F-flotufolastat in men with low PSA biochemical recurrence after radical prostatectomy. Identifier: NCT06604442. Updated September 11, 2025. Accessed March 2, 2026. https://clinicaltrials.gov/study/NCT06604442
- Helfand B. An intra-patient contemporaneous comparison of 18F-piflufolastat and 18F-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. J Clin Oncol. 2026;44(7_suppl):32.
