Synthesis and evaluation of a thymidine analog for positron emission tomography study of tumor DNA proliferation in vivo

Abstract

This study describes the synthesis, radiolabelling and biological evaluation of 5-(2,4-difluoro-5-[18F]fluoromethyl-phenyl)-2- hydroxymethyl-tetrahydrofuran-3-ol, 13. Radiolabelling was achieved by reaction of the tosylate 3 with K[18F] in the presence of Kryptofix 222. Good stability in saline and serum solutions at physiological temperatures in vitro was observed. A cell incorporation study of 13 using SW1222 tumor cells showed a linear uptake, unfortunately, in vivo studies indicated that 13 was undergoing defluorination. Rapid defluorination of the radiotracer was confirmed by an in vitro stability study in blood plasma. Finally, a comparison between the DNA uptake of 13 and tritiated th..