F-PSMA-11 Versus Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial.

Background: Fluorine-18 (F)-labelled prostate-specific membrane antigen (PSMA) offers several advantages over gallium-68 (Ga) in terms of costs, yield, transport/distribution, and image resolution.

Objective: This trial investigates the new radiotracer F-PSMA-11 via a prospective, intraindividual crossover design. The trial was powered for noninferiority of F-PSMA-11 over Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) in terms of the number of positive PET scans. Secondary endpoints were as follows: (1) superiority of F-PSMA-11 over Ga-PSMA-11 with respect to the number of positive PET scans, the total number of suspicious prostate cancer lesions, and the miPSMA expression score of corresponding lesions; (2) correlation of the PET/CT images with available follow-up data for F-PSMA-11 and Ga-PSMA-11; and (3) assessment of the interobserver variability.

Design, Setting, And Participants: Prostate cancer patients (primary or biochemical recurrence) were randomised in a double-blind crossover design whereby each patient received both F-PSMA-11 and Ga-PSMA-11 PET/CT.

Outcome Measurements And Statistical Analysis: All scans were reviewed and scored by three independent experienced nuclear physicians following the proposed guideline for the interpretation of PSMA-ligand PET/CT, as described by Eiber et al. RESULTS AND LIMITATIONS: In total, 82 patients were included for scan analyses. The primary endpoint was met: per patient, the proportions of positive scans rated by the three readers were 67%/67%, 65%/65%, and 73%/70% for F-PSMA-11/Ga-PSMA-11 PET/CT. The miPSMA expression score was higher for F-PSMA-11 than for Ga-PSMA-11 for the reference reader. Follow-up data showed identical estimated sensitivity for both the F-PSMA-11 and the Ga-PSMA-11 scan (0.92, 0.83, and 0.92 for the three readers). A fair to good agreement among readers (at patient level) was obtained, which was demonstrated by a Light's kappa value of 0.59 for both tracers.

Conclusions: The tracer F-PSMA-11 is noninferior toGa-PSMA-11. Superiority of F-PSMA-11 was limited to the miPSMA expression score, given by the reference reader. Inter-rater agreement was fair to good, and equal for both radiotracers.

Patient Summary: In this study, we compared two radiotracers: F-PSMA-11 and Ga-PSMA-11. We proved that F-PSMA-11 is not inferior to Ga-PSMA-11 for detecting prostate cancer and thus can be used as an alternative. Possible superiority of this tracer should be further investigated in specific subpopulations.