SYNTHESIS OF 3'-FLUORO-3'-DEOXYTHYMIDINE AND STUDIES OF ITS F-18 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 F-18 to be used to monitor this drug's biodistribution and targeting. A new synthesis for FDT, suited for F-18 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 F-18 potassium fluoride and crown-18 ether yielded the F-18-labeled fluoro derivative which on detritylation afforded F-18 FDT with 7% labeling efficiency. This is the first reported synthesis of 3'-fluoro-5'-O-trityl deoxythymidine using potassium fluoride and preparing its F-18 labeled analog. The time required to incorporate F-18 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.