Doctoral Degrees (Nuclear Medicine)
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Browsing Doctoral Degrees (Nuclear Medicine) by Subject "Disease -- Animal models"
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Item Open Access In-house prepared ⁹⁹ᴹTc-ethylenedicysteinedeoxyglucose in mice, rabbits and baboons: tumour, local infection/inflammation and normal biodistribution(University of the Free State, 2015) Horn-Lodewyk, J.; Otto, A. C.; Zeevaart, J. R.𝑬𝒏𝒈𝒍𝒊𝒔𝒉 This thesis covers the research to evaluate the normal-, tumour- and infection/inflammation biodistribution properties of the in-house prepared 99mTc- Ethylenedicysteine-deoxyglucose (IHP 99mTc-EC-DG) in nude mice, New Zealand White rabbits and baboons (Papio Ursinus). In the South African context there is a need for a low cost, widely available, single photon emission glucose metabolism imaging agent that can detect cancerous tumours and infection/inflammation (IFI/IF), since health care funding is problematic in the country. Fluorine-18-flurodeoxyglucose (18F-FDG) comes close to the ideal tumour detection radiopharmaceutical, but has certain shortcomings e.g. short physical half-life (no late imaging possible), high cost and non-specific. Yet 18F-FDG biodistribution to IFI/IF and tumours are similar and pose a differentiation limitation of these two specific diseases. In the search for the ideal radiopharmaceutical for tumour/IFI/IF detection, The South African Nuclear Energy Corporation (Necsa) developed two different labelling routes, of ethylenedicysteine-deoxyglucose (EC-DG) with 99mTc that could be locally prepared at the Department of Nuclear Medicine at the Universitas Academic hospital. The summation of different diseases and physiological conditions present in humans can be replicated by the use of animal models for research. Three different species of animals were utilised to obtain the necessary research data that contributed to the evaluation of the diagnostic potential of the IHP 99mTc-EC-DG. All three animal species showed increased biodistribution of the IHP 99mTc-EC-DG to the liver (critical organ) and heart. IHP 99mTc-ECDG demonstrated rapid clearance by the kidneys seen as a decrease in background activity in animals on the scintigraphic images. The IHP 99Tc-EC-DG images showed no biodistribution to the brain in the larger animal models. This is the greatest difference between the biodistribution of IHP 99mTc-EC-DG visually compared to clinical 18F-FDG studies (in the literature) which shows high brain uptake. The conclusion can be made that the IHP 99mTc-EC-DG does not pass over the blood brain barrier (BBB) in accordance with earlier literature findings. The IHP 99mTc-EC-DG showed similar uptake to 18F-FDG in lung tumours induced in nude mice. There are similarities between the uptake of the IHP 99mTc-EC-DG and the 99mTc-ECDG described in the literature by Yang et al. (2003:470-471). This includes biodistribution to lung tumours, biodistribution to the liver and heart and excretion by the kidney. IHP 99mTc-EC-DG uptake in septic- (Escherichia coli) and sterile (zymosan) IFI/IF induced in New Zealand White rabbits was evaluated and compared to 67Ga-citrate uptake. IHP 99mTc- EC-DG is dependent on a cellular response and mainly uses this mechanism for uptake in IFI/IF, whereas 67Ga-citrate has multiple mechanisms of uptake. IHP 99mTc-EC-DG is taken up in low grade cellular IFI/IF. Early diagnosis of low grade- (zymosan) and bacterial IFI/IF is possible with IHP 99mTc-EC-DG. The IHP 99mTc-EC-DG could be a much cheaper and more affordable diagnostic alternative than 18F-FDG and 67Ga-cirate for tumour and IFI/IF imaging. From the research covered in this thesis, there is no doubt that the IHP 99mTc-EC-DG exhibits promising detection characteristics for both IFI/IF and specific tumours thus warranting human clinical trials. Furthermore, IHP 99mTc-EC-DG’s has future potential to improve diagnosis and prognosis, planning and monitoring of cancer treatment in humans and must be investigated further. ___________________________________________________________________