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

OBJECTIVES

[(18)F]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [(18)F]-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 [(18)F]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [(18)F]-FMAU in comparison with conventional thermal conditions.

METHODS

A simplified one-pot synthesis of [(18)F]-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-[(18)F]fluoro-1,3,5-tri-O-benzoyl-d-arabinofuranose ([(18)F]-sugar) and bis-2,4-(trimethylsilyloxy)-5-methyluracil (silylated uracil) in the presence of a Friedel-Crafts catalyst, trimethylsilyl trifluoromethanesulfonate (TMSOTf).

RESULTS

Microwave significantly enhanced the coupling efficiency of [(18)F]-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 [(18)F]-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.

CONCLUSIONS

A reliable microwave-assisted approach has been developed for routine synthesis of [(18)F]-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 [(18)F]-FMAU can be readily achieved under new reaction conditions.