18F-PSMA-11 Versus 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial

Abstract

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

Objective: This trial investigates the new radiotracer ¹⁸F-PSMA-11 via a prospective, intraindividual crossover design. The trial was powered for noninferiority of ¹⁸F-PSMA-11 over ⁶⁸Ga-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 ¹⁸F-PSMA-11 over ⁶⁸Ga-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 ¹⁸F-PSMA-11 and ⁶⁸Ga-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 ¹⁸F-PSMA-11 and ⁶⁸Ga-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 ¹⁸F-PSMA-11/⁶⁸Ga-PSMA-11 PET/CT. The miPSMA expression score was higher for ¹⁸F-PSMA-11 than for ⁶⁸Ga-PSMA-11 for the reference reader. Follow-up data showed identical estimated sensitivity for both the ¹⁸F-PSMA-11 and the ⁶⁸Ga-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 ¹⁸F-PSMA-11 is noninferior to⁶⁸Ga-PSMA-11. Superiority of ¹⁸F-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: ¹⁸F-PSMA-11 and ⁶⁸Ga-PSMA-11. We proved that ¹⁸F-PSMA-11 is not inferior to ⁶⁸Ga-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.

Keywords: (18)F-PSMA-11; (68)Ga-PSMA-11; Biochemical recurrence; Positron emission tomography/computed tomography; Prostate cancer; Staging.