Effective Preparation of [18F]Flumazenil Using Copper-Mediated Late-Stage Radiofluorination of a Stannyl Precursor

(1) Background: [F-18]Flumazenil 1 ([F-18]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABA(A) in the brain. The production of [F-18]FMZ 1 for its clinical use has proven to be challenging, requiring harsh radiochemical conditions, while affording low radiochemical yields. Fully characterized, new methods for the improved production of [F-18]FMZ 1 are needed. (2) Methods: We investigate the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of [F-18]FMZ 1 that is suitable for clinical use. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. (3) Results: The radiosynthesis of [F-18]FMZ 1 was fully automated using the iPhase FlexLab radiochemistry module, affording a 22.2 +/- 2.7% (n = 5) decay-corrected yield after 80 min. [F-18]FMZ 1 was obtained with a high radiochemical purity (>98%) and molar activity (247.9 +/- 25.9 GBq/mu mol). (4) Conclusions: The copper-mediated radiofluorination of the stannyl precursor is an effective strategy for the production of clinically suitable [F-18]FMZ 1.

Automated summary

This study investigates the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of clinically suitable [F-18]FMZ 1. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. The fully automated synthesis of [F-18]FMZ 1 using the iPhase FlexLab radiochemistry module yielded a high radiochemical purity and molar activity.