title: Microwave-assisted one-pot radiosynthesis of 2'-deoxy-2'-[18F]fluoro-5-methyl-1-β-d-arabinofuranosyluracil ([18F]-FMAU).
abstract: OBJECTIVE
  [(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.
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-9061, USA. chenkai@usc.edu
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Zibo
authors.initials: Z
authors.lastname: Li
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D005462:Fluorine Radioisotopes; D008872:Microwaves; D011854:Radiochemistry
chemical_list: D005462:Fluorine Radioisotopes; D001086:Arabinofuranosyluracil; C034935:clevudine