On the 99mTc-labeling of isoniazid with different 99mTc cores

Recent advances in the chemistry of radiolabeling with Tc-99m such as use of the Tc-99m tricarbonyl and Tc-99m-HYNIC cores have revived interest in Tc-99m-labeling of small biomolecules and further investigation as potential radiopharmaceuticals. Isoniazid, a drug commonly used for treatment of tuberculosis, has been chosen for the present study. Three distinct strategies were utilized to radiolabel isoniazid with Tc-99m. In the direct labeling protocol, the hydrazino amide functional group of isoniazid was used for Tc-99m-labeling in the HYNIC sense using tricine and EDDA as co-ligands. The other strategies of Tc-99m-labeling involved the derivatization of isoniazid to its N, N-diacetic acid derivative, which in turn was either used as a tridentate ligand for labeling with the [(TC)-T-99m(CO)(3)(H2O)(3)](+) synthon or directly labeled by the conventional route wherein Tc-99m is in the +3 oxidation state. The complexes prepared in > 95% yields were characterized by paper chromatography, thin layer chromatography and HPLC. Comparison of the three approaches showed that maximum specific activity and stability was obtained in the Tc-99m-isoniazid derivative synthesized via the tricarbonyl method. However, in vitro cell-binding studies indicated that none of the Tc-99m-isoniazid complexes prepared had any appreciable uptake in Mycobacterium tuberculosis. Copyright (c) 2005 John Wiley & Sons, Ltd.