title: On the isolation and evaluation of a novel unsubstituted 5-nitroimidazole derivative as an agent to target tumor hypoxia.
abstract: The presence and extent of hypoxic regions in cancerous tissue bears a negative influence on the effectiveness of radiation therapy and chemotherapy of the cancer hence estimation of hypoxia is an important problem. Several (99m)Tc-labeled nitroimidazole-based non-invasive agents have been tried for this purpose but none had optimal characteristics and the search continues. Herein we report, for the first time to the best of our knowledge, the isolation, (99m)Tc(CO)(3) labeling and evaluation of an unsubstituted 5-nitroimidazole derivative obtained as a side product during the synthesis of 4-nitroimidazole derivative. The (99m)Tc(CO)(3)-labeled complex of 5-nitroimidazole derivative could be prepared in excellent yield under mild conditions. Its evaluation in fibrosarcoma tumor bearing Swiss mice showed uptake and slow clearance of injected activity from tumor. The tumor-to-muscle ratio was found to be very high but tumor-to-blood ratio greater than 1 could not be obtained throughout the limited time point study. The study revealed that complex under investigation has features similar to other 2-nitroimidazole complexes so far as the retention of injected activity in tumor is concerned.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra 400085, India.
authors.forename: Madhava B
authors.initials: MB
authors.lastname: Mallia
authors.forename: Suresh
authors.initials: S
authors.lastname: Subramanian
authors.forename: Anupam
authors.initials: A
authors.lastname: Mathur
authors.forename: H D
authors.initials: HD
authors.lastname: Sarma
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds