Synthesis, ^99m Tc-tricarbonyl Labeling And Biodistribution Studies Of Pegylated Nitroimidazoles

Many variable-structured nitroimidazole derivatives have been explored as 99mTc-labeled tumor hypoxia imaging agents. However, until now, no 99mTc-labeled nitroimidazole complex has been widely used in clinic for tumor hypoxia imaging.This work designed and synthesized 8 new nitroimidazole derivatives, whose structure contained nitroimidazole as targeting molecule, pegylated linker and different tridentates (BPA. AOPA or IDA) for radiolabeling. The ligands were reacted with [99mTc(CO)3]+ core very effectively. The result complexes had high RCP (>90%), good stability at room temperature and good hydrophilicity.Biodistribution studies in tumor-bearing mice indicated that the tumor uptake and retention of 99mTc(CO)3-labeled 2-nitroimidazoles was not so good. They were excreted via renal (and hepatobiliary) route. The tumor/blood and tumor/muscle ratios were both dissatisfactory. The change in 99mTc-chelate, pegylation linker and triazole introduction all had effects on biological properties. However, the extended pegylation linker and triazole introduction hadn't improved the pharmaceutical properties as expected. [99mTc(CO)3(IDA-PEG,-NIM)]- and [99mTc(CO)3(AOPA-PEG3-NIM)] had relatively better tumor uptake and tumor/muscle ratios, which suggested their potential value for further studies as tumor hypoxia imaging agents.