Synthesis and biodistribution of novel 99mTc labeled 4-nitroimidazole dithiocarbamate complexes as potential agents to target tumor hypoxia

Abstract

Sodium 3-(4-nitro-1H-imidazolyl)propyl dithiocarbamate (N4IPDTC) was synthesized and radiolabelled with a [^99mTcO]³⁺, [^99mTcN]²⁺ or [^99mTc(CO)₃]⁺ core to produce ^99mTcO-N4IPDTC, ^99mTcN-N4IPDTC and ^99mTc(CO)₃-N4IPDTC, respectively. All of the three complexes were prepared with high radiochemical purity and had good in vitro stability over a period of 6 h. The partition coefficient results showed that ^99mTcO-N4IPDTC and ^99mTcN-N4IPDTC were lipophilic, while ^99mTc(CO)₃-N4IPDTC was hydrophilic. The tumor cell experiments and the biodistribution in mice bearing S180 tumors showed that all of the complexes exhibited good hypoxic selectivity and accumulation in the tumor. Among them, ^99mTcO-N4IPDTC had the advantages of higher tumor uptake, and higher tumor/blood and tumor/muscle ratios. Planar scintigraphic imaging studies showed there was a visible accumulation in tumor sites, suggesting its potential usefulness as a tumor hypoxia imaging agent.