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

Abstract

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 -t-1) was prepared by reaction of CaCl 2 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′-[ 34 m Cl]-2′-ClUdR was similarly prepared using [ 34 m Cl]-MgCl 2 or [ 34 m Cl]-Dowex 21-K resin in 2.7% (16.8 MBq mmol −1) and 36% (0.304 GBq mmol −1) radiochemical yield respectively.