Radiosynthesis of F-18 labeled cytidine analog 2′-fluoro-5-iodo-l-β-d-arabinofuranosylcytosine ([¹⁸F]FIAC)

We reported the synthesis of 2′-deoxy-2′-[¹⁸F]fluoro-5-iodo-1-β-d-arabinofuranosyl-5-iodo-cytosine ([¹⁸F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[¹⁸F]fluoro-1,3,5-tri-O-benzoyl-α-d-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The ¹⁸F-fluorosugar was converted to 1-bromo-¹⁸F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable β-anomer selectivity (α/β=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the β-[¹⁸F]FIAC with high radiochemical purity (≥98%).