Direct labeling of isoniazid with technetium-99m for diagnosis of tuberculosis

Isonicotinic acid hydrazide (isoniazid) is one of the most effective agents in tuberculosis therapy. Hence it was chosen as ligand for Tc-99m labeling and imaging in the developed animal model with a gamma camera. Direct labeling of isoniazid with technetium-99m was studied. Factors affecting the radiolabeling efficiency such as amount of reducing agent, pH and time of the reaction were studied. Biodistribution of the labeled compound was performed in Sprague-Dawley rats. The localization kinetics of the radiolabeled complex was also studied in the developed animal model by injecting 100-125 MBq Tc-99m-isoniazid intravenously in the ear of rabbit and the images were taken with a gamma camera. Optimum conditions gave > 98% labeling efficiency of Tc-99m-isoniazid. Biodistribution studies in rats revealed that the maximum uptake was in kidneys (15%, 8% and 2.5% at 0.5, 4 and 24 hours, respectively), indicating renal excretion of the Tc-99m-isoniazid. High accumulation was obtained in liver (10%, 11% and 4% at 0.5, 4 and 24 hours, respectively) and significant radioactivity was also seen in the intestines (8%, 6% and 1% at 0.5, 4 and 24 hours, respectively), indicating hepatobiliary excretion of the complex. Less than 2% uptake in stomach until 24 hours confirmed good in vivo stability of the complex. Tc-99m-isoniazid initially accumulated in infective lesions of S. aureus in rabbits due to hyper-vascularity, but because of its non specificity for S. aureus the residency of Tc-99m-isoniazid was low and it showed rapid wash out from the lesion, whereas residency of tubercular lesion was high and it remained in the tubercular lesion in the delayed images also. The results suggest that Tc-99m-isoniazid is a specific agent for localization of tubercular lesions.