99mTc/Re complexes bearing bisnitroimidazole or mononitroimidazole as potential bioreductive markers for tumor: Synthesis, physicochemical characterization and biological evaluation

Four monoamine-monoamide dithiol (MAMA) ligands containing two or one nitroimidazole moieties were synthesized and labeled with 99mTc (labeling yield > 95%). The proposed structures of 99mTc-complexes are identified by comparison with analogous Re-MAMA complexes. 99mTc-MAMA complexes show better physicochemical characters than 99mTcO-(PnAO-1-(2-nitroimidazole)). Reduction potentials of nitro groups of the rhenium complexes are within the range for bioreductive compounds. As expected, biodistribution studies demonstrate that the 2-nitroimidazole complex shows better tumor-to-tissue ratios than 4-nitroimidazole analog for mononitroimidazole complexes, but not for MAMA-bisnitroimidazoles due to higher lipophilicity. Both the bisnitroimidazole compounds show rapider excretion, lower background activity in liver and higher tumor-to-tissue ratios than the mononitroimidazoles. Better biodistribution characteristic makes both the MAMA-bisnitroimidazole complexes, especially 99mTc-15, be potential tumor hypoxia marker.

A series of oxotechnetium and oxorhenium complexes containing two or one nitroimidazole groups were synthesized and evaluated in vitro and in vivo as potential bioreductive markers for tumor.Figure optionsDownload as PowerPoint slideHighlights
► New ReO- and 99mTcO-complexes with bis- or mono-nitroimidazole groups were synthesized.
► Bioreductive capacities of the compounds were evaluated both in vitro and in vivo.
► Bisnitroimidazole compounds showed improved biodistribution results than mononitroimidazoles.
► Compound 99mTc-15 serves as potential tumor hypoxia imaging agent for further study.