A fully automated synthesis of [18F]-FEAU and [18F]-FMAU using a novel dual reactor radiosynthesis module

2'-Deoxy-2'-[F-18]fluoro-5-substituted-1-beta-D-arabinofuranosyluracils, including 2'-deoxy-2'-[F-18]fluoro-5-methyl-1-beta-D-arabinofuranosyluracil [F-18]FMAU and [F-18]FEAU are established radiolabeled probes to monitor cellular proliferation and herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression with positron emission tomography. For clinical applications, a fully automated CGMP-compliant radiosynthesis is necessary for production of these probes. However, due to multiple steps in the synthesis, no such automated synthetic protocols have been developed. We report here a fully automated synthesis of [F-18]-FEAU and [F-18]-FMAU on a prototype dual reactor module TRACERlab FX FN. The synthesis was performed by using a computer-programmed standard operating procedure, and the product was purified on a semipreparative high-performance liquid chromatography (HPLC) integrated with the synthesis module using 12% EtOH in 50 mM Na2HPO4. Finally, the percentage of alcohol was adjusted to 7% by adding Na2HPO4 and filtered through a Millipore filter to make dose for human. The radiochemical yield on the fluorination was 40 +/- 10% (n = 10), and the overall yields were 4 +/- 1% (d. c.), from the end of the bombardment; [18F]FEAU (n = 7) and [F-18]FMAU (n = 3). The radiochemical purity was > 99%, specific activity was 1200-1300 mCi/mu mol. The synthesis time was 2.5 h. This automated synthesis should be suitable for production of [F-18]FIAU, [F-18]FFAU, [F-18]FCAU, [F-18]FBAU and other 5-substitued thymidine analogues.