99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia.

ABSTRACT

In this study, the commercially available secnidazole was successfully converted to secnidazole xanthate (SNXT), in which the xanthate group can act as a bifunctional chelator to coordinate with 99mTc. 99mTc-nitrido complex of SNXT(99mTcN-SNXT) and 99mTc-oxo complex of SNXT(99mTcO-SNXT) were prepared with high radiochemical purity. Both of the complexes were found to be stable in vitro and to exhibit similar hydrophilicity. In addition, comparative in vitro cell uptake studies under anoxic and normoxic conditions demonstrated that both agents were preferentially taken up by hypoxic cells. Biodistribution studies in mice bearing S180 tumor showed 99mTcO-SNXT exhibited a higher tumor uptake and tumor-to-muscle ratio than 99mTcN-SNXT. Furthermore, in SPECT imaging study, 99mTcO-SNXT exhibited a clear accumulation in tumor at 2 h post-injection, suggesting its potential to be a novel hypoxia imaging agent.