Comparing hypoxia-targeting potential of 99mTc(CO)3-labeled 2-nitro and 4-nitroimidazole

✍ Scribed by Madhava B Mallia; Suresh Subramanian; Anupam Mathur; H.D. Sarma; Meera Venkatesh; Sharmila Banerjee

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 157 KB
• Volume: 51
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1525

✦ Synopsis

Non-invasive determination of hypoxia is an important problem in clinical nuclear medicine. Although 18 F-fluoromisonidazole is used clinically for hypoxia determination, the short half-life (t 1/2 = 109.77 min), high cost and less availability of cyclotrone-produced 18 F make 99m Tc (t 1/2 = 6 h)-based agents more desirable. With this aim, 99m Tc(CO) 3 -labeled iminodiacetic acid derivatives of 2-and 4-nitroimidazole are investigated for their ability to target hypoxic tumors. A bifunctional chelating agent, N, N-bis[(tert-butoxycarbonyl)methyl]-2-bromoethylamine, was synthesized in the first step, which was then conjugated to the nitroimidazoles in the second step. The tert-butyl ester derivatives formed were hydrolyzed to obtain the iminodiacetic acid derivatives of corresponding nitroimidazoles. The radiolabeling of the iminodiacetic acid derivatives with [ 99m Tc(CO) 3 (H 2 O) 3 ] 1 core was carried out following a reported protocol. Biodistribution of the prepared complexes was carried out in Swiss mice bearing fibrosarcoma tumor. The 2-nitroimidazole complex showed a steady retention in activity ($1.5% injected dose per gram [%ID/g]) in tumor throughout the period of study (3 h) indicating that it may be localized in the hypoxic cells. The 4-nitroimidazole counterpart, however, showed an initial uptake of $4.6%ID/g at 30 min post injection, which was then observed to wash out rapidly.