Synthesis and evaluation of 2‐, 4‐, 5‐substituted nitroimidazole‐iminodiacetic acid‐^99mTc(CO)₃ complexes to target hypoxic tumors

Abstract

Abstract Determination of hypoxia in tumor is an important problem in the clinical management of cancer. Towards this, a series of differently substituted nitroimidazoles, viz. 2‐nitro, 4‐nitro and 5‐nitroimidazole iminodiacetic acid (IDA) derivatives were synthesized and radio‐labeled with a [ 99m Tc(CO) 3 (H 2 O) 3 ] + core. The corresponding 185/187 Re(CO) 3 analogue of 2‐nitroimidazole‐IDA‐ 99m Tc(CO) 3 complex was also prepared and characterized to elucidate the mode of bonding between the ligand and the M(CO) 3 core ( M = 99m Tc, 185/187 Re). All the three nitroimidazole‐IDA‐ 99m Tc(CO) 3 complexes could be prepared in over 95% yield determined by HPLC. The three complexes were then evaluated in a suitable animal model bearing tumor. Though the in vivo accumulation of complexes in hypoxic tissue is governed by factors such as lipophilicity, charge, etc., the variation in accumulation in hypoxic tissue, in the present case, could be explained by considering the reported values of single electron reduction potential of the respective nitroimidazoles. Among the three derivatives studied, the 2‐nitroimidazole‐IDA‐ 99m Tc(CO) 3 complex produced the best result followed by the 5‐nitroimidazole complex. Copyright © 2010 John Wiley & Sons, Ltd.