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

(1) Background: [ 18 F]Flumazenil 1 ([ 18 F]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 [ 18 F]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 [ 18 F]FMZ 1 are needed. (2) Methods: We investigate the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of [ 18 F]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 [ 18 F]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. [ 18 F]FMZ 1 was obtained with a high radiochemical purity (>98%) and molar activity (247.9 ± 25.9 GBq/µmol). (4) Conclusions: The copper-mediated radiofluorination of the stannyl precursor is an effective strategy for the production of clinically suitable [ 18 F]FMZ 1 .