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Title of Thesis

Samina Roohi
Institute/University/Department Details
Department of Biochemistry/ Quaid-i-Azam University, Islamabad
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
technetium-99m, nuclear medicine, infection specific radiopharmaceuticals, inflammation, vancomycin, kanamycin, isoniazid

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 ‰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.

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4949.46 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
328.25 KB
2 1 Introduction 1
1651.9 KB
  1.1 Nuclear Medicine 1
  1.2 Technetium-99m 7
  1.3 Radiopharmaceuticals 21
  1.4 Infections And Inflammations 33
  1.5 Antibiotics 48
  1.6 Vancomycin 52
  1.7 Kanamycin 57
  1.8 Isoniazid 64
  1.9 Aims And Objectives 70
3 2 Materials And Methods 71
454.99 KB
  2.1 Production Of Technetium-99m 71
  2.2 Synthesis, Quality Control And Biodistribution Of 99m TC- Conjugates In A Model Of Bacterial Infection 83
4 3 Results 92
823.98 KB
  3.1 Synthesis And Biodistribution Of 99m TC-Vancomycin In Model Of Bacterial Infection 92
  3.2 Synthesis, Quality Control And Biodistribution Of 99m -Tc-Kanamycin 109
  3.3 Direct Labeling Of Isoniazid With Technetium-99m And Its Quality Control 127
5 4 Discussion 142
180.55 KB
6 5 Conclusions 149
1771.64 KB
  5.1 References 151
  5.2 Annexure 151
  5.3 Publications 163