title: ⁹⁹mTc/Re complexes bearing bisnitroimidazole or mononitroimidazole as potential bioreductive markers for tumor: synthesis, physicochemical characterization and biological evaluation.
abstract: Four monoamine-monoamide dithiol (MAMA) ligands containing two or one nitroimidazole moieties were synthesized and labeled with (99m)Tc (labeling yield > 95%). The proposed structures of (99m)Tc-complexes are identified by comparison with analogous Re-MAMA complexes. (99m)Tc-MAMA complexes show better physicochemical characters than (99m)TcO-(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 (99m)Tc-15, be potential tumor hypoxia marker.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Mei
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Taiwei
authors.initials: T
authors.lastname: Chu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002627:Chemistry, Physical; D055664:Electrochemical Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D051381:Rats; D012211:Rhenium / Q000737:chemistry*; D012513:Sarcoma, Experimental / Q000737:chemistry* / Q000378:metabolism; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D012211:Rhenium; D013667:Technetium