Radiosynthesis and evaluation of novel [99mTc(I)]+ and [99mTc(I)(CO)3]+ complexes with a 4‐nitroimidazole isocyanide for imaging tumor hypoxia

Abstract

[99mTc(I)]+ and [99mTc(I)(CO)3]+ complexes with isocyanide exhibit high stability, which makes them suitable platforms to develop novel 99mTc radiopharmaceuticals. To develop novel 99mTc radiotracers for imaging hypoxia, in this study, a novel L ligand (4‐nitroimidazole isocyanide derivative) was synthesized and labelled using [99mTc(I)]+ core and [99mTc(I)(CO)3]+ core to produce [99mTc(L)6]+ and [99mTc(CO)3(L)3]+ with high yields. To verify the structure of the 99mTc complexes, corresponding rhenium analogues were synthesized and characterized. Both of the 99mTc complexes were stable and hydrophilic. in vitro cellular uptake results showed they could exhibit good hypoxic selectivity. The evaluation of biodistribution in mice bearing S180 tumors indicated both of them could accumulate in tumor. Between them, [99mTc(L)6]+ exhibited higher tumor uptake and tumor/non‐target ratio than [99mTc(CO)3(L)3]+. Further, single photon emission computed tomography (SPECT) imaging studies of [99mTc(L)6]+ indicated an obvious accumulation in tumor and the value of the region‐of‐interest (ROI) ratio of the uptake for the tumor site to the corresponding non‐tumor region was 5.64 ± 0.52. The above results suggested [99mTc(L)6]+ would be a potential tracer for imaging tumor hypoxia.