Synthesis of 3'-fluoro-3'-deoxythymidine and studies of its 18F-radiolabeling, as a tracer for the noninvasive monitoring of the biodistribution of drugs against AIDS

Article abstract of DOI:10.1016/S0022-1139(00)82356-8

3'-Fluoro-3'-deoxy-thymidine (FDT), a fluorinated analog of 3'-azido-thymidine (AZT), is both more active against the HIV virus but also more toxic than AZT.Because of its fluorine atom, it can be labeled with 18F to be used to monitor this drug's biodistribution and targeting.A new synthesis for FDT, suited for 18F labeling, has been developed.After protecting the 5'-hydroxy group with a trityl group, the 3'-hydroxy group was substituted with a mesyl group in the lyxo configuration.Treatment with 18F potassium fluoride and crown-18 ether yielded the 18F-labeled fluoro derivative which on detritylation afforded 18F FDT with 7percent labeling efficiency.This is the first reported synthesis of 3'-fluoro-5'-O-trityl deoxythymidine using potassium fluoride and preparing its 18F labeled analog.The time required to incorporate 18F in the intermediate compound and isolate the end-product is reasonably short (approximately 2 h) which will allow sufficient time to conduct biological studies with this short-lived radionuclide.