Preclinical Evaluation of ^99mTc-Ethambutol, an Alternative Tuberculosis Diagnostic Tool

Abstract

^99mTc-ethambutol was preclinically evaluated as an alternative diagnostic tuberculosis agent. Its radiochemical purity, stability in saline and serum, in vitro Mycobacterium tuberculosis (MBT) binding, and biodistribution in mice were studied, and targeted imaging in model rabbits was performed. The following labeling conditions were found to be optimum: 3 mg of EMB, 150 µg of stannous fluoride, 3 mCi of sodium pertechnetate, pH 5.6. The highest product yield was reached in the time interval 30–90 min after reconstitution. The relative content of ^99mTc-EMB in normal saline at room temperature decreased to 90 ± 0.25% in 240 min. ^99mTc-EMB was stable in vitro in serum at 37°C, with 16.8 ± 0.3% radioimpurities accumulated in 16 h. ^99mTc-EMB showed 69.8 ± 1.5% in vitro uptake in live strains of MBT. High in vivo accumulation (15.5 ± 0.8% ID) of the labeled EMB was observed in the infected site of model mice as compared to the normal and inflamed (muscles) sites. High uptake in the MBT infected site of a model rabbit was seen scintigraphically at 120 min after the intravenous administration of the ^99mTc-EMB. Stability in normal saline and serum, substantial in vitro MBT uptake, high in vivo accumulation in the infected site, and accurate scintigraphy of the infected site make ^99mTc-EMB promising as a novel alternative diagnostic tool for tuberculosis.