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

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 18 F to be used to monitor this drug's biodistribution and targeting. A new synthesis for FDT, suited for 18 F labeling, has been developed. After protecting the 5′-hydroxy group with a trityl group, the 3′-hydroxy group was subtituted with a mesyl group in the lyxo configuration. Treatment with 18 F potassium fluoride and crown-18 ether yielded the 18 F-labeled fluoro derivative which on detritylation afforded 18 F FDT with 7% labeling efficiency. This is the first reported synthesis of 3′- fluoro-5′-O-trityl deoxythymidine using potassium fluoride and preparing its 18 F labeled analog. The time required to incorporate 18 F 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.