Synthesis and evaluation of [99mTcN]2+ core and [99mTcO]3+ core labeled complexes with 4-nitroimidazole xanthate derivative for tumor hypoxia imaging

A 4-nitroimidazole xanthate ligand (NMXT) was synthesized and radiolabeled with [(TcN)-Tc-99m](2) core and [(TcO)-Tc-99m](3+) core to obtain (TcN)-Tc-99m-NMXT and (TcO)-Tc-99m-NMXT, respectively. The two Tc-99m-complexes were prepared with high radiochemical purity and had good stability. The partition coefficient results indicated both of them were hydrophilic, and cellular uptake studies showed they exhibited good hypoxic selectivity. From the biodistribution study results, (TcO)-Tc-99m-NMXT showed more favourable tumor uptake (1.73 +/- 0.14 ID%/g) and higher tumor/muscle ratio (7.01 +/- 0.16) than (TcN)-Tc-99m-NMXT at 4 h post-injection. Single photon emission computed tomography (SPECT) imaging study of (TcO)-Tc-99m-NMXT showed there was a visible accumulation in tumor site, suggesting it would be a promising candidate as a tumor hypoxia imaging agent.