Synthesis and biological evaluation of 99mTc-ECF. A new ethionamide derivative for tuberculosis diagnosis

In this work we propose a technetium-99m-labeled derivative from Ethionamide (ETH), further referred to as 99mTc-ECF for tuberculosis diagnosis. The biological features of this radioactive agent have been studied. The 2-ethylpyridine-4-carbothioamide-ferrocene (ECF) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that 99mTc-ECF is obtained with high radiolabelling yield (>90 %). Radiochemical analysis of 99mTc-ECF revealed that the molecule was efficiently labeled with a little free remaining pertechnetate. Only 1-2 % of the tracer was leached out from the complex at 24 h when incubated in serum at 37 deg C which confirmed its high stability. The sensitivity test of ECF showed that the group of grafted ferrocenyl does not seem to have largely altered the active site of the molecule. In-vitro investigations were conducted using BCG (Bacille Calmette-Guerin) as analogue of Mycobacterium Tuberculosis and Listeria Monocytogenes as negative control. It was proved that for BCG, ECF has kept the bacteriostatic properties of the parent compound (ETH). In physiological conditions, the measured up-take of the tracer with live bacteria was about 24.1 and 7.1 % for BCG and Listeria Monocytogenese, respectively. The comparison of the 99mTc-ECF accumulation at sites of BCG infected animals, which is expressed as target-to-non-target ratio (found to be equal to 2.15) with other radiotracers was discussed. This allowed us to consider that 99mTc-ECF could be a reasonable radiotracer for mycobacterial infections. Obtained results were good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work. (author)