In-house prepared 99mTc-ethylenedicysteinedeoxyglucose in mice, rabbits and baboons: tumour, local infection/inflammation and normal biodistribution

[摘要] English: This thesis covers the research to evaluate the normal-, tumour- andinfection/inflammation biodistribution properties of the in-house prepared 99mTc-Ethylenedicysteine-deoxyglucose (IHP 99mTc-EC-DG) in nude mice, New Zealand Whiterabbits and baboons (Papio Ursinus). In the South African context there is a need for alow cost, widely available, single photon emission glucose metabolism imaging agent thatcan detect cancerous tumours and infection/inflammation (IFI/IF), since health carefunding is problematic in the country. Fluorine-18-flurodeoxyglucose (18F-FDG) comesclose 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-FDGbiodistribution to IFI/IF and tumours are similar and pose a differentiation limitation ofthese two specific diseases. In the search for the ideal radiopharmaceutical fortumour/IFI/IF detection, The South African Nuclear Energy Corporation (Necsa) developedtwo different labelling routes, of ethylenedicysteine-deoxyglucose (EC-DG) with 99mTc thatcould be locally prepared at the Department of Nuclear Medicine at the UniversitasAcademic hospital.The summation of different diseases and physiological conditions present in humans can bereplicated by the use of animal models for research. Three different species of animalswere utilised to obtain the necessary research data that contributed to the evaluation ofthe diagnostic potential of the IHP 99mTc-EC-DG.All three animal species showed increased biodistribution of the IHP 99mTc-EC-DG to theliver (critical organ) and heart. IHP 99mTc-ECDG demonstrated rapid clearance by thekidneys 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 animalmodels. This is the greatest difference between the biodistribution of IHP 99mTc-EC-DGvisually compared to clinical 18F-FDG studies (in the literature) which shows high brainuptake. The conclusion can be made that the IHP 99mTc-EC-DG does not pass over theblood 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 nudemice. There are similarities between the uptake of the IHP 99mTc-EC-DG and the 99mTc-ECDGdescribed in the literature by Yang et al. (2003:470-471). This includes biodistributionto 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 inNew 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 inIFI/IF, whereas 67Ga-citrate has multiple mechanisms of uptake. IHP 99mTc-EC-DG is takenup in low grade cellular IFI/IF. Early diagnosis of low grade- (zymosan) and bacterialIFI/IF is possible with IHP 99mTc-EC-DG.The IHP 99mTc-EC-DG could be a much cheaper and more affordable diagnostic alternativethan 18F-FDG and 67Ga-cirate for tumour and IFI/IF imaging. From the research covered inthis thesis, there is no doubt that the IHP 99mTc-EC-DG exhibits promising detectioncharacteristics 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.

[发布机构] University of the Free State