title: A novel amine-dioxime chelator for technetium-99m: synthesis and evaluation of 2-nitroimidazole-containing analogues as markers for hypoxic cells.
abstract: A novel amine-dioxime chelator for (99m)Tc has been developed. It offers the advantages of ease of synthesis and flexibility in alteration of lipophilicity. Labeling by stannous reduction of pertechnetate takes place rapidly and efficiently at room temperature and is stable for 24 h. The (99m)Tc:ligand ratio is believed to be 1:2. Seven different alkyl moieties were used to achieve a range of lipophilicities. Three series of compounds were prepared: 2-nitroimidazoles as potential hypoxia-targeting agents, 4-nitroimidazoles as a less easily reduced isomer, and untargeted anilines. In an in vitro model of cellular hypoxia, the 2-nitroimidazole compounds all showed selective accumulation whereas 4-nitroimidazoles showed variable selectivity and aniline showed no selectivity. These experiments demonstrate the potential utility of the 2-nitroimidazole derivatives of the amine-dioxime class of chelator as hypoxia-targeting agents.
authors.affiliation: Departments of Medical Biophysics and Pharmaceutical Sciences, University of Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Z F
authors.initials: ZF
authors.lastname: Su
authors.forename: J R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: A M
authors.initials: AM
authors.lastname: Rauth
authors.forename: D N
authors.initials: DN
authors.lastname: Abrams
authors.forename: M W
authors.initials: MW
authors.lastname: Billinghurst
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006224:Cricetinae; D007202:Indicators and Reagents; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D010091:Oximes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D002614:Chelating Agents; D007202:Indicators and Reagents; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals; C044310:technetium Tc 99m propylene amine oxime