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

2′-Deoxy-2′-[¹⁸F]fluoro-5-substituted-1-β-D- arabinofuranosyluracils, including 2′-deoxy-2′-[¹⁸F] fluoro-5-methyl-1-β-Darabinofuranosyluracil [¹⁸F]FMAU and [ ¹⁸F]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 [¹⁸F]-FEAU and [¹⁸F]-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 50mM Na ₂HPO₄. 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 [ ¹⁸F]FMAU (n = 3). The radiochemical purity was >99%, specific activity was 1200-1300 mCi/lmol. The synthesis time was 2.5 h. This automated synthesis should be suitable for production of [¹⁸F]FIAU, [ ¹⁸F]FFAU, [¹⁸F]FCAU, [¹⁸F]FBAU and other 5-substitued thymidine analogues.