BARC/PUB/08/0545

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

Mallia, M. B.; Subramanian, S.; Mathur, A.; Sarma, H. D.; Venkatesh, M.; Banerjee, S.

ABSTRACT

Non-invasive determination of hypoxia is an important problem in clinical nuclear medicine. Although 18F-fluoromisonidazole is used clinically for hypoxia determination, the short half-life (t1/2 = 109.77 min), high cost and less availability of cyclotrone-produced 18F make 99mTc(t1/2 = 6 h)-based agents more desirable. With this aim, 99mTc(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 [99mTc(CO)3(H2O)3]+ 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.

 
 
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