Synthesis and biological evaluation of novel 99mTc-oxo and 99mTc-tricarbonyl complexes with C3-functionalized thymidine dithiocarbamate for tumor imaging

A novel C3-functionalized thymidine dithiocarbamate derivative (3'DTC-TdR) was successfully synthesized and labelled using [(TcO)-Tc-99m](3+) core and [Tc-99m(CO)(3)(H2O)(3)](+) core with high yields. The structures of the Tc-99m complexes were verified by preparation and characterization of the corresponding stable rhenium complexes. Both of the complexes were lipophilic and stable in vitro. Cell internalization experiments indicated that the uptakes of (TcO)-Tc-99m-3'DTC-TdR were related to nucleoside transporters. Biodistribution of these complexes in mice bearing tumor showed that they had high tumor uptakes, good tumor/muscle ratios and tumor/blood ratios. Especially for (TcO)-Tc-99m-3'DTC-TdR, it exhibited the highest tumor/muscle ratio and tumor/blood ratio at 4h post-injection. SPECT/CT imaging studies indicated clear accumulation in tumor, suggesting (TcO)-Tc-99m-3'DTC-TdR would be a promising candidate for tumor imaging.