Abstract
Background: Infections pose a signifi cant risk to immunocompromised individuals, and accurate,effi cient diagnosis remain challenging. Current imaging methods like MRI and FDG PET lack pathogenspecifi city which complicate diagnosis and lead to overuse of antibiotics. Recent data shows that[18F]fl uoromannitol ([18F]FMtl) is sensitive and specifi c to infection in vivo by exploiting the pathogen-specifi c mannitol transporter. This work aims to establish a reliable, automated method for producing[18F]fl uoromannitol to facilitate clinical research studies in human subjects.

Results: This study optimized and automated the radiosynthesis of [¹⁸F]fl uoromannitol ([¹⁸F]FMtl) on aTrasis AllinOne synthesizer. The 105-minute synthesis achieved an average yield of 11.0% (n=19) with>97% radiochemical purity, and the product remained stable for at least 8 hours. While yield was lowerthan the previously reported manual method, automation enabled reproducibility and sterility. Processimprovements included optimizing evaporation steps and reaction temperature, which signifi cantlyincreased fl uorine incorporation and yield. The process was validated to meet USP <823> regulatoryrequirements including full QC testing on three consecutive batches.

Conclusions : An automated method for the radiochemical synthesis of [18F] fluoromannitol wasdeveloped and optimized on a commercially available Trasis AllinOne radiosynthesizer. This methodallows for the reliable production and global dissemination of [18F]FMtl for use in clinical research trials.

Automated Radiosynthesis of [18F] Fluoromannitolfor Clinical Research on a Commercially AvailableTrasis AllinOne Radiosynthesizer