Microwave-assisted one-pot radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-d-arabinofuranosyluracil ([18F]-FMAU)

Objectives[18F]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [18F]-FMAU synthesis are time-consuming, resulting in low radiochemical yield and inconvenient applications for the clinic. We have previously reported the use of Friedel-Crafts catalysts for an improved synthesis of [18F]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [18F]-FMAU in comparison with conventional thermal conditions.MethodsA simplified one-pot synthesis of [18F]-FMAU was developed under microwave conditions. Various reaction times, temperatures, and microwave powers were systematically explored to optimize the coupling reaction of 2-deoxy-2-[18F]fluoro-1,3,5-tri-O-benzoyl-d-arabinofuranose ([18F]-sugar) and bis-2,4-(trimethylsilyloxy)-5-methyluracil (silylated uracil) in the presence of a Friedel-Crafts catalyst, trimethylsilyl trifluoromethanesulfonate (TMSOTf).ResultsMicrowave significantly enhanced the coupling efficiency of [18F]-sugar and silylated uracil by reducing the reaction time to 10 min (6-fold reduction as compared to conventional heating) at 95 °C. Base hydrolysis followed by high-performance liquid chromatography purification produced the desired [18F]-FMAU. The overall radiochemical yield was 20 ± 4% (decay corrected, n = 3). Radiochemical purity was > 99% and specific activity was > 400 mCi/μmol. The α/β anomer ratio was 1:2. The radiosynthesis time was about 90 min from the end of bombardment.ConclusionsA reliable microwave-assisted approach has been developed for routine synthesis of [18F]-FMAU. The new approach affords a simplified process with shorter synthesis time and higher radiochemical yield as compared to conventional heating. A fully automated microwave-assisted synthesis of [18F]-FMAU can be readily achieved under new reaction conditions.