99mTc-N-IFC: a new isoniazid derivative for Mycobacterium diagnostic

Abstract

Abstract We present in this work a new technetium-99m-labeled derivative from isoniazid. The labeling was achieved with a double-ligand transfer through the use of a ferrocene derivative. A further referred to as 99mTc-N-IFC (N-Isonicotinamide ferrocene carboxamide labeled with 99mTc), targeting infections in experimental animals, has been synthesized. The N-IFC was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that it was obtained with high radiolabelling yield (95%). Radiochemical analyses of 99mTc-N-IFC revealed that the molecule was efficiently labeled with a little free pertechnetate in the preparations containing purified compound. Only 1–2% of the tracer was leached out from the complex at 24 h when incubated in serum at 37 ºC confirmed its high stability. The radiolabeled complex was found to be 10% bound to blood protein, which corresponds to a fast retention advantage. Biodistribution study showed the renal route of excretion and has also demonstrated that our radiolabeled compound is rapidly and significantly accumulated (P<0.5) at infection sites. Thigh model of localized infection was prepared in mice by injecting of BCG (pGFM-11) (fluorexcente BCG) live bacteria in growing phase. The confirmation of the bacteria presence in infection sites has been established through its fluorescence characteristic. The comparison of the 99mTc-N-IFC accumulation at sites of BCG (pGFM-11) infected animals, which is expressed as target-to-non-target ratio, (3.14) with other radiotracers was discussed. This allowed us to consider that 99mTc-N-IFC could be a good radiotracer for mycobacterial infections. Obtained results were in good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work.