On the isolation and evaluation of a novel unsubstituted 5-nitroimidazole derivative as an agent to target tumor hypoxia

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 19; pp. 5233 - 5237
• Main Authors: Mallia, Madhava B., Subramanian, Suresh, Mathur, Anupam, Sarma, H.D., Venkatesh, Meera, Banerjee, Sharmila
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-10-2008; Elsevier
• Subjects: 5-Nitroimidazole; 99mTc; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Disease Models, Animal; Hypoxia; Hypoxia - drug therapy; Medical sciences; Mice; Molecular Structure; Neoplasms - drug therapy; Nitroimidazoles - chemical synthesis; Nitroimidazoles - chemistry; Nitroimidazoles - pharmacology; Organotechnetium Compounds - chemical synthesis; Organotechnetium Compounds - chemistry; Organotechnetium Compounds - pharmacokinetics; Pharmacology. Drug treatments; Tumor; Hypoxia; Tumor; 99mTc; 5-Nitroimidazole; Nitro compound; Imidazole derivatives; Oxygen; 99mTC; Rodentia; Organic ligand; Transition metal Carbonyl Complexes; Uptake; Technetium Carbonyl Complexes; Diagnostic agent; Tissue; Vertebrata; Mammalia; Mouse; Scintigraphic agent; Animal; Distribution; Radioisotopic product; Chemical synthesis
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.08.069

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
99mTc-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,
99mTc(CO)
3 labeling and evaluation of an unsubstituted 5-nitroimidazole derivative obtained as a side product during the synthesis of 4-nitroimidazole derivative. The
99mTc(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.