The synthesis of radiolabelled 1-(2'-fluoro-2'-deoxy-β-D-ribofuranosyl)-uracil and 1-(2'-chloro-2'-deoxy-β-D-ribofuranosyl)uracil

Radiolabelled derivatives of 1-(2'fluoro-2'-deoxy-β-D-ribofuranosyl)uracil 3 (2'-FUdR) and 1-(2'-chloro-2'-deoxy-β-D-ribofuranosyl)uracil 4(2'-ClUdR) were synthesized for evaluation as diagnostic radiopharmaceuticals. 6-[3H]-2'-FUdR (21% radiochemical yield from 6-[3H]-uridine; 4.26 GBq mmol-1) and 2-[14C]-2'-FUdR (25% radiochemical yield; 1.85 GBq mmol-1) were prepared by reaction of anhydrous hydrogen fluoride (AHF) with 6-[3H]- or 2-[14C]-labelled 2,2'-anhydro-1-β-D-arabinofuranosyluracil 2 (2,2'-AUR). 6-[3H]-2'-ClUdR (53% radiochemical yield; 11.1 GBq mmol-1) was prepared by reaction of CaCl2 with 6-[3H]-2,2'-AUR. Reaction of [18F]-AHF with 2,2'-AUR afforded 2'-[18F]-2'-FudR in low radiochemical yield while reaction of 2,2'-AUR with [36Cl]-NaCl and trifluoroacetic acid gave 2'-[36Cl]-2'-ClUdR (30% radiochemical yield; 5.46 MBq mmol-1). 2'-[sup(34m)Cl]-2'-ClUdR was similarly prepared using [sup(34m)Cl]-MgCl2 or [sup(34m)Cl]-Dowex 21-K resin in 2.7% (16.8 MBq mmol-1) and 36% (0.304 GBq mmol-1) radiochemical yield respectively. (author)