title: Synthesis and biological characterisation of novel dithiocarbamate containing 5-nitroimidazole (99m)Tc-complexes as potential agents for targeting hypoxia.
abstract: With the aim to develop new potential (99m)Tc-radiopharmaceuticals for imaging hypoxia based on the formation of Tc-nitrido complexes, two novel dithiocarbamate containing metronidazole derivatives (L1 and L2) have been prepared and characterised. The synthesis of L1 and L2 was achieved in excellent yield and high purity. Labelling with (99m)Tc was successfully performed using a low ligand concentration (approximately 2-3mg) and the desired products were obtained with high radiochemical purity (>90%). Lipophilicity, plasma protein binding, and biodistribution in normal- and tumour-bearing-CD1 mice studies were performed to asses the potentiality for nuclear medicine oncology. According to the physicochemical and biological behaviour both in healthy animals and in animals bearing solid tumours complex dtcTc1 could be considered as a starting point for the development of new radiopharmaceuticals for imaging hypoxia.
authors.affiliation: Cátedra de Radioquímica, Facultad de Química, Gral Flores 2124, Universidad de la República, 11800 Montevideo, Uruguay.
authors.forename: Javier
authors.initials: J
authors.lastname: Giglio
authors.forename: Soledad
authors.initials: S
authors.lastname: Fernández
authors.forename: Ana
authors.initials: A
authors.lastname: Rey
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
mesh_terms: D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry*; D015687:Cell Hypoxia; D008795:Metronidazole / Q000737:chemistry; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging*; D009593:Nitroimidazoles / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002219:Carbamates; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D008795:Metronidazole; C052587:4-nitroimidazole