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العنوان
Radiolabeling of Some Antimicrobial Compounds
for Inflammation Imaging and its BiologicalEvaluation in Mice
المؤلف
Bekheet, Safaa Bekheet Mohamed.
هيئة الاعداد
باحث / Safaa Bekheet Mohamed Bekheet
مشرف / Ibrahim Hassan Borai
مشرف / Hala Mostafa Ghanem
مناقش / Mohamed Abdel-MotalebAbdel-Rahman
الموضوع
Biochemistry Department.
تاريخ النشر
2015.
عدد الصفحات
p 238. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Biochemistry
الناشر
تاريخ الإجازة
1/1/2015
مكان الإجازة
جامعة عين شمس - كلية العلوم - الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

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Abstract

Radiopharmaceuticals may be defined as a chemical or pharmaceutical compounds were labeled with a radionuclide in tracer quantities, used as a diagnostic or therapeutic purpose of human diseases. Radiopharmaceuticals agents are usually administrated into a vein. Depending on which type of scan is being performed the imaging will be done either immediately, a few hours later or even several days after injection. The active ingredient that is the actual radiolabeled chemical is usually present in trace amount below the amount necessary to initiate any physiological response in an individual.
The characteristics of an ideal radioisotope for therapy are quite different from those required for imaging. For imaging, the radioisotopes energy must be suitable for the camera crystal, without significant absorption by the tissue. Whereas, the energy of a therapeutic radioisotope must be deposited in the tissue to damage the DNA chains to keep the diseased cells from replicating.
Radiopharmaceuticals are determined by which part of the body is under study since some compounds collect in specific organs better than others. Since due to the radiopharmaceutical compounds are usually administrated to humans so they must be subjected to all quality control tests such as radiochemical purity to ensure necessary purity, safety and efficiency of these products for the intended nuclear medicine applications.
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 or 111In-labeled leucocytes, 99mTc polyclonal immunoglobin and 99mTc labeled antibiotics. Radiolabeled compounds are injected intravenously and accumulated in the inflammatory lesion.
The theoretical advantage of using antimicrobial agents as the localizing agent for infective foci is the selective toxicity of the 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. In this study we will mention method for labeling the compounds with technetium-99m, also the different methods used for separation and purification of labeled compounds.
Radiolabeling of Some Antimicrobial Compounds for Inflammation Imaging and its Biological Evaluation in Mice is divided into three parts:
The first part: is an introduction concerning the radiopharmaceuticals development, chromatography technique for separation and their uses to resist inflammation, definition, types of inflammation and structure, mode of action for the compounds of teicoplanin, ceftazidime and erythrocin.
The second part: contains detailed information concerning the chemicals, reagents, the radionuclide, the equipments and the counting system used in this study. It describes the labeling method by using technetium-99m for teicoplanin, ceftazidime and erythrocin using stannous chloride dihydrate as reducing agent.
The third part: evaluation of some biochemical parameters, inflammation markers in normal and inflamed mice with living microbe and results of biodistribution of the labeled compounds in experimental animals bearing sterile, in sterile inflammation.
The obtained results showed that:
The labeling of teicoplanin, ceftazidime and erythrocin compounds by using a simple method were obtained by the reaction of them with technetium-99m in the presence of stannous chloride dihydrate as reducing agent at pH 9, 10 and10, respectively. The reaction mixture was incubated at room temperature for 30 minutes.
1) The effect of the amounts of teicoplanin, ceftazidime and erythrocin on the radio chemical yields proved that small amounts of them yielded low radiochemical yields of labeled compounds. Increasing the amounts of teicoplanin, ceftazidime and erythrocin until reached 2, 1 and 5 mg, respectively, produced a high radiochemical yields which equals 87.7, 86.5 and 85%, respectively.
2) The effect of the amounts of stannous chloride dihydrate on the radiochemical yields of 99mTc-teicoplanin, 99mTc-ceftazidime and 99mTc-erythrocin revealed that the radiochemical yields increased by increasing the stannous chloride dihydrate amount up to 5, 10 and 5 μg, respectively, then with continuous increasing the yield decreased due to colloid formation from reduced technetium and reduced stannous.
3) The effect of the pH of the reaction mixture on the radiochemical yields of 99mTc-teicoplanin, 99mTc-ceftazidime and 99mTc-erythrocin revealed that high radiochemical yields of 87.7%, 86.5% and 85%, respectively, were obtained at pH 9, 10 and 10, respectively, and that the radiochemical yields decreased in acidic or alkaline media due to increase colloid formation.
4) The effect of the reaction time on the radiochemical yields of 99mTc-teicoplanin, 99mTc-ceftazidime and 99mTc-erythrocin revealed that increasing the reaction time to 30 minutes, increased the radiochemical yields. The labeled compounds were stable up to 2 h after labeling.
5) The effect of the reaction temperature on the radiochemical yields of 99mTc-teicoplanin, 99mTc-ceftazidime and 99mTc-erythrocin revealed that the optimum temperature that’s give high radiochemical yields is room temperature 25˚C. By increasing the reaction temperature the radiochemical yields decreased due to thermal decomposition of the labeled compounds.
6) The separation and purification of the labeled compounds by thin layer chromatography and electrophoresis were done. Filtration of the labeled compounds using millipore filter 0.22 µ size was done.
7) Evaluation of some biochemical parameters and inflammation markers such as:(ALT, AST, Urea, Creatinine, Albumin, Total Protein, Complement 3, Complement 4, LDH, CPK, CRP, ESR, CBC) in normal and inflamed mice by living microbe. The results revealed that increasing in the kidney and liver function test results and inflammation markers after inflammation induction than in normal mice.
8) The in-vivo biodistribution studies of the labeled compounds 99mTc-teicoplanin, 99mTc-ceftazidime and 99mTc-erythrocin in the experimental animals showed the ability of the tracer to bind to the infectious foci more than aseptic inflammation bearing mice (heat killed bacteria and turpentin oil) at different time intervals with a ratio of abscess to muscle (target to non target, T/NT) equal 4.33 after 2 h for teicoplanin, 5.06 and 4.12% after 1 h for ceftazidime and erythrocin, respectively. .