[(99m)~Tc(CO)_3]^+ labeled histidine derivative containing 4-nitroimidazole:Synthesis,biodistribution as a tumor hypoxia imaging agent

A novel histidine derivative containing 4-nitroimidazole,(S)-2-(4-((4-nitro-1H-imidazol-1-yl) methyl) benzamido)-3-(1H-imidazol-4-yl)propanoic acid (His-NI),was synthesized and labeled with [99mTc(CO)3(H2O)3]+.The tricarbonyl technetium complex,the 99mTc(CO)3-His-NI,showed a 99% yield under mild conditions at a low His-NI ligand concentration of 10-4 molL-1,and its biodistribution in mice bearing S180 tumor had a selective accumulation in tumor (2.01±0.40%ID/g at 1 h postinjection) and a slow clearance.The tumor/muscle ratio was 1.64 at 1 h,3.10 at 4 h,and 3.88 at 24 h,indicating that the 99mTc(CO)3-His-NI has a potential to image tumor hypoxia.

A novel histidine derivative containing 4-nitroimidazole, （S）-2-（4-（（4-nitro-1H-imidazol-1-yl） methyl） benzamido） -3- （1H- imidazol-4-yl）propanoic acid （His-N1）, was synthesized and labeled with [^99mTc（CO）3（H2O）3]^＋. The tricarbonyl technetium complex, the ^99mTc（CO）3-His-NI, showed a 99% yield under mild conditions at a low His-NI ligand concentration of 10^-4 mol·L^-1, and its biodistribution in mice bearing S180 tumor had a selective accumulation in tumor （2.01±0.40 %ID/g at 1 h postinjection） and a slow clearance. The tumor/muscle ratio was 1.64 at 1 h, 3.10 at 4 h, and 3.88 at 24 h, indicating that the ^99mTc（CO）3-His-NI has a potential to image tumor hypoxia.