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

BACKGROUND

Infections pose a significant risk to immunocompromised individuals, and accurate, efficient diagnosis remain challenging. Current imaging methods like MRI and FDG PET lack pathogen specificity which complicate diagnosis and lead to overuse of antibiotics. Recent data shows that [F]fluoromannitol ([F]FMtl) is sensitive and specific to infection in vivo by exploiting the pathogen-specific mannitol transporter. This work aims to establish a reliable, automated method for producing [F]fluoromannitol to facilitate clinical research studies in human subjects.

RESULTS

This study optimized and automated the radiosynthesis of [F]fluoromannitol ([F]FMtl) on a Trasis 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 lower than the previously reported manual method, automation enabled reproducibility and sterility. Process improvements included optimizing evaporation steps and reaction temperature, which significantly increased fluorine incorporation and yield. 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 [F]fluoromannitol was developed and optimized on a commercially available Trasis AllinOne radiosynthesizer. This method allows for the reliable production and global dissemination of [F]FMtl for use in clinical research trials.