Automated Radiosynthesis of [18F]Fluoroedaravone for Clinical Research on a Commercially Available Trasis AllinOne Radiosynthesizer

Abstract Background Measuring reactive oxygen and nitrogen species (RONS) in vivo remains challenging to date, thereby limiting our understanding of the role oxidative stress plays in neurodegenerative disease pathogenesis. Current PET tracers developed to detect RONS face limitations in biological stability, blood-brain barrier permeability, and RONS specificity. A novel PET tracer for RONS, [ 18 F]fluoroedaravone ([¹⁸F]FEDV), was recently reported that demonstrates high contrast in vivo with high specificity for RONS. The previously reported synthesis of [ 18 F]FEDV was performed manually, therefore, the goal of this study was to develop and optimize a robust and reproducible automated method for the synthesis of [ 18 F]FEDV on a commercially available Trasis AllinOne (AiO) radiosynthesizer for routine preclinical and clinical research use. Results The [¹⁸F]FEDV synthesis was adapted from a manual protocol into a fully automated two-pot, three-step process on the Trasis AiO radiosynthesizer. Optimization included varying precursor masses, radiofluorination times, temperatures, dilution conditions, purification and reformulation parameters. The optimized synthesis and purification process was completed in 105 min and produced [¹⁸F]FEDV with a radiochemical yield of 11.4% ± 1.5% (n = 50), radiochemical purity of 97.5% ± 1.4% (n = 25), chemical impurities < 100 µg/dose, and a pH of 5.0. This automated process produced [¹⁸F]FEDV with high reproducibility and reliability suitable for clinical use. The process was validated to meet USP < 823 > regulatory requirements including full QC testing on three consecutive batches. Conclusions An automated method for the radiochemical synthesis of [ 18 F]fluoroedaravone was developed and optimized on a commercially available Trasis AiO radiosynthesizer. This method allows for the reliable production of [ 18 F]FEDV for supporting preclinical research and first in human clinical trials.