DEVELOPMENT OF LABELED THYMIDINE ANALOGS FOR IMAGING TUMOR PROLIFERATION

We have sought nucleoside analogs suitable for labeling with F-18 that could be used to image tumor proliferation with positron emission tom ography (PET). The following three thymidine analogs were labeled with tritium and screened for their catabolism and biodistribution in vivo in mice: 5-fluoro-1-(2 '-deoxy-2 '-fluoro-beta-D-ribofuranosyl)uracil (FFUdR), 5-fluoro-1-(2 '-deoxy-2 '-fluoro-beta-D-arabinofuranosyl)ura cil (FFaraU) and 5-methyl-1-(2 '-deoxy-2 '-fluoro-beta-D-ribofuranosyl )uracil (FTdR). We found that all three compounds were stable to degra dation in vivo and when incubated in blood. Of the three analogs teste d, only FFUdR showed preferential retention in rapidly proliferating t issues, such as the spleen and implanted tumors, and it attained tissu e to blood ratios of 2.1 at 2 h.