Novel 99mTc labelled complexes with 2-nitroimidazole isocyanide: design, synthesis and evaluation as potential tumor hypoxia imaging agents.

Abstract

Radiolabelled 2-nitroimidazoles have been used for imaging hypoxia. With the aim of developing novel 99mTc radiotracers for imaging hypoxia, four novel 2-nitroimidazole isocyanide derivatives (2a, 2b, 2c, and 2d) were synthesized and radiolabelling was carried out for preparing their corresponding 99mTc complexes. These 99mTc complexes were stable in vitro and could exhibit good hypoxic selectivity. The partition coefficient results indicated that they were hydrophilic, and an evaluation of biodistribution in mice bearing S180 tumors indicated that all of the complexes could accumulate in the tumors. Among them, 99mTc-2c exhibited the highest tumor uptake and tumor/blood and tumor/muscle ratios at 2 h post-injection. Further, single photon emission computed tomography (SPECT) imaging studies indicated clear accumulation in tumors, suggesting that 99mTc-2c was a promising candidate for hypoxia imaging.