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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-09, Vol.27 (18)
• Main Authors: Haskali, Mohammad B, Roselt, Peter D, O’Brien, Terence J, Hutton, Craig A, Ali, Idrish, Vivash, Lucy, Jupp, Bianca
• Format: Article
• Language: English
• Subjects: Flumazenil; GABA; Hallucinogenic drugs; Instrument industry
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27185931

(1) Background: [[sup.18]F]Flumazenil 1 ([[sup.18]F]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABA[sub.A] in the brain. The production of [[sup.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 [[sup.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 [[sup.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 [[sup.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. [[sup.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 [[sup.18]F]FMZ 1.