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

Abstract

AbstractNon‐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. Copyright © 2008 John Wiley & Sons, Ltd.