Automated synthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-d-arabinofuranosyluracil ([18F]-FMAU) using a one reactor radiosynthesis module

2′-Deoxy-2′-[18F]fluoro-5-methyl-1-β-d-arabinofuranosyluracil ([18F]-FMAU) is an established PET probe used to monitor cellular proliferation. For clinical applications, a fully automated cGMP-compliant radiosynthesis would be preferred. However, the current synthesis of [18F]-FMAU requires a multistep procedure, making the development of an automated protocol difficult and complicated. Recently, we have developed a significantly simplified one-pot reaction condition for the synthesis of [18F]-FMAU in the presence of Friedel-Crafts catalysts. Here, we report a fully automated synthesis of [18F]-FMAU based on a one reactor radiosynthesis module using our newly developed synthetic method. The product was purified on a semi-preparative high-performance liquid chromatography integrated with the synthesis module using 6% EtOH in 10 mM phosphate buffer or 8% MeCN/water. [18F]-FMAU was obtained in 12±3% radiochemical yield (decay corrected overall yield based on [18F]-F−, n=4) with 383±33 mCi/μmol specific activity at the time of injection. The α/β anomer ratio was 4:6. The overall reaction time was about 150 min from the end of bombardment and the radiochemical purity was >99%. This automated synthesis should also be suitable for the production of other 5-substituted thymidine analogues.