Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections. Established techniques such as radio labeled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals.
The objective of this study was to radiolabel some common drugs with Technetium-99m (99mTc) having potential for medical use and evaluate their potential as infection imaging agents in animal models. For this purpose, antibiotics Vancomycin, Kanamycin and Isoniazid were labelled with 99mTc and their potential as infection imaging agent for diagnosis of infection was evaluated.
Labelling of the drugs with 99mTc was achieved using SnC12H2O as reducing agent. The optimum conditions for labelling and the effects of various factors such as ligand/ reductant ratio, pH, and incubation times were also studied. Radiochemical purity and stability of 99mTc-vancomycin, 99mTc-kanamycin and 99mTc-isoniazid was determined by thin layer chromatography. Biodistribution studies of labelled complexes were performed in a model of bacterial infection in Sprague-Dawley rats. In-vitro binding of 99mTc-kanamycin and 99mTc-vancomycin to Saureus bacteria was assessed. For comparison, binding of 99mTc-Ciprofloxacin to bacteria was also determined. The localization kinetics of the radiolabelled 99mTc-Kanamycin and 99mTc-Isoniazid was studied in the infected animal model by intravenous injection of radio labeled complex and the images were taken with Gamma camera.
The results show that labelling efficiency in all three drugs is >95% at optimum conditions. The resulting complexes are quite stable and labelling efficiency of â‰¥95% is maintained for up to 6 hours. Only 2 to 3.5% of the tracer leached out from the 99mTc-kanamycin after 24 hours when incubated in serum at 37 oC, confirming its high stability. The in-vitro binding of 99mTc-vancomycin and 99mTc-kanamycin to S.aureus bacteria was comparable to 99mTc-ciprofloxicin (40 to 65%).
Our studies have shown that 99mTc-vancomycin localized to bacterial infection only and did not localize to sterile inflammation significantly. The target thigh/normal thigh radioactivity ratio also indicated a higher binding affinity to the infection induced with S. aureus.
Scintigraphy shows that S. aureus infection in infected rabbit thigh was visualized as an area of increased tracer accumulation just after injection of 99mTc-kanamycin.
Our studies have also shown that Mycobacterium tuberculosis infection in rabbits thigh could be visualized as early as 2 hours after administration of 99mTc-INH and remained clear visible till 12 hrs.
The direct methods of labelling of vancomycin, kanamycin and isoniazid with 99mTc were exploited, which are simple, rapid, efficient and do not require bifunctional chelating agents. Due to the ease of 99mTc-kanamycin and 99mTc-vancomycin preparation and infection uptake, it may provide an alternative to 99mTc-ciprofloxacin in a variety of patients referred for infection evaluation. 99mTc-isoniazid complex developed in our laboratory is shown to be a stable, reproducible and safe preparation with high labeling efficiency, having specific accumulation in Mycobacterium Tuberculosis. Therefore 99mTc-INH can be an important radiopharmaceutical in the detection and follow up of tubercular lesions in patients with tuberculosis.