Radiolabeling of Some Antimicrobial Compounds for Inflammation Imaging and its Biological Evaluation in Mice

Abstract

Radiopharmaceuticals play a major role in providing the best possible solutions for inflammation diagnosis and treatment. In the last few decades, a large number of radiopharmaceuticals are developed for imaging of infection and inflammation such as 67Ga-citrate, 99mTc polyclonal immunoglobin, 99mTc or 111In-labeled leucocytes and 99mTc labeled antibiotics. Radiolabeled compounds are injected intravenously and accumulated in the inflammatory lesion due to locally changed physiological condition after administration, the excretion occurs by glomerular filtration and tubular secretion within 24 hour being almost totally eliminated. The theoretical advantage of using antimicrobial agents as the localizing agent for infective foci is the selective toxicity of the labeled compound for microbial rather than human targets. Such agents should therefore be able to distinguish between inflammation due to infection with microbial pathogens and inflammation due to injury or autoimmune disease where microbes are not involved. The antimicrobial agents have the potential to influence clinical decision in the management of complicated conditions such as fever of unknown origin or occult infections. Antibiotics are chemical substances which produced by some microorganisms and have capability to deactivate or kill other microorganisms, generally infection causing bacteria. On the basis of their specificity towards microorganisms, antibiotics can be classified either as bactericides or as bacteriostatic. Bactericides antibiotics were used for killing bacteria only while bacteriostatic antibiotics are not killing them but slow down their rate of growth. Out interest around three antibiotics which were teicoplanin, ceftazidime and erythromycin. The aim of this work was firstly, labeling of teicoplanin, ceftazidime and erythromycin with technetium-99m. In addition the factors affecting the labeling reaction were optimized to obtain the labeled compounds in the highest radiochemical yield. Secondly, studied some biochemical parameters and inflammation markers in normal and inflamed mice with living bacteria. Thirdly, studied the biodistribution of the labeled compounds in normal and inflamed mice with living bacteria (septic inflammation), with dead bacteria and turpentine oil (aseptic inflammation). The labeled compounds (99mTc-teicoplanin,99mTc-ceftazidime and 99mTc-erythromycin) were prepared by the reaction of them with technetium-99m in the presence of stannous chloride dihydrate as reducing agent, the reaction was incubated at room temperature (25˚C) for 30 minutes, then the radiochemical yield of the labeled compounds were determinated using thin layer chromatography and electrophoresis techniques.