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

Abstract

Abstract2′‐Deoxy‐2′‐[18F]fluoro‐5‐substituted‐1‐β‐D‐arabinofuranosyluracils, including 2′‐deoxy‐2′‐[18F]fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil [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 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 [18F]FMAU (n=3). The radiochemical purity was >99%, specific activity was 1200–1300 mCi/µmol. 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. Copyright © 2009 John Wiley & Sons, Ltd.