Microwave-assisted one-pot radiosynthesis of 2 '-deoxy-2 '-[F-18]fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([H-18-FMAU)

作者：Chen Kai^*; Li Zibo; Conti Peter S

来源：Nuclear Medicine and Biology, 2012, 39(7): 1019-1025.

DOI：10.1016/j.nucmedbio.2012.03.003

• Microwave-assisted
• [F-18]-FMAU
• PET probe
• Friedel-Crafts catalyst
• Automated synthesis

Objectives: [F-18]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [F-18]-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 [F-18]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [F-18]-FMAU in comparison with conventional thermal conditions.
Methods: A simplified one-pot synthesis of [F-18]-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-[F-18]fluoro-1,3,5-tri-O-benzoyl-o-arabinofuranose ([F-18]-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 [F-18]-sugar and silylated uracil by reducing the reaction time to 10 min (6-fold reduction as compared to conventional heating) at 95 degrees C. Base hydrolysis followed by high-performance liquid chromatography purification produced the desired [F-18]-FMAU. The overall radiochemical yield was 20 +/- 4% (decay corrected, n = 3). Radiochemical purity was >99% and specific activity was >400 mCi/mu mol. The alpha/beta 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 [F-18]-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 [F-18]-FMAU can be readily achieved under new reaction conditions.

• 出版日期2012-10