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

Abstract

Abstract 2′‐Deoxy‐2′‐[ 18 F]fluoro‐5‐substituted‐1‐ β ‐ D ‐arabinofuranosyluracils, including 2′‐deoxy‐2′‐[ 18 F]fluoro‐5‐methyl‐1‐ β ‐ D ‐arabinofuranosyluracil [ 18 F]FMAU and [ 18 F]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 [ 18 F]‐FEAU and [ 18 F]‐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 Na 2 HPO 4 . Finally, the percentage of alcohol was adjusted to 7% by adding Na 2 HPO 4 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; [ 18 F]FEAU ( n =7) and [ 18 F]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 [ 18 F]FIAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and other 5‐substitued thymidine analogues. Copyright © 2009 John Wiley & Sons, Ltd.