Preparation of two ^99mTc(CO)₃ labelled complexes with a 4-nitroimidazole isocyanide at different temperatures for molecular imaging of tumor hypoxia

A 4-nitroimidazole isocyanide derivative (6) was synthesized and radiolabelled with ^99mTc(CO)₃ core in high yield. It was interesting to note that ^99mTc(CO)₃-6a and ^99mTc(CO)₃-6b can be prepared at 100 °C and 25 °C, respectively. ^99mTc(CO)₃-6a had three 6 molecules while ^99mTc(CO)₃-6b contained two 6 molecules. The corresponding rhenium complexes were prepared to confirm the structure of the ^99mTc complexes. Both complexes showed good stability in vitro and hypoxic selectivity. The partition coefficient results indicated both of them were hydrophilic and ^99mTc(CO)₃-6a was more hydrophilic than ^99mTc(CO)₃-6b. From the biodistribution study results, ^99mTc(CO)₃-6a showed higher tumor/blood and tumor/muscle ratios at 2 h post-injection. Further, single photon emission computed tomography (SPECT) imaging study of ^99mTc(CO)₃-6a showed there was an observable tumor uptake, suggesting it would be a potential tracer for imaging of tumor hypoxia. (author)