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dc.contributor.advisorOtto, A. C.
dc.contributor.advisorZeevaart, J. R.
dc.contributor.authorHorn-Lodewyk, J.
dc.date.accessioned2016-01-13T11:08:41Z
dc.date.available2016-01-13T11:08:41Z
dc.date.issued2015-02
dc.identifier.urihttp://hdl.handle.net/11660/2193
dc.description.abstractEnglish: 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.en_ZA
dc.description.abstractAfrikaans: Hierdie tesis handel oor navorsing om die normale-, tumor- en infeksie/inflammasie biodistribusie eienskappe van in-huis voorbereide 99mTc-etileendisisteïen-deoksiglukose (IHP 99mTc-EC-DG) in naakte muise, Nieu-Seelandse wit konyne en bobbejane (Papio Ursinus) te evalueer. In die Suid-Afrikaanse konteks is daar 'n behoefte vir 'n lae koste, algemeen beskikbare, enkelfoton emissie glukosemetabolisme beeldingsmiddel wat kankeragtige tumors en infeksie/inflammasie (IFI/IF) kan waarneem, omdat die befondsing van gesondheidsdienste problematies is in die land. Fluoor-18-fluorodeoksiglukose (18F-FDG) is amper die ideale tumor deteksie radiofarmaseutiese middel, maar dit het sekere tekortkominge, bv. 'n kort fisiese halfleeftyd (geen laat beelding moontlik), hoë koste en dit is nie-spesifiek. Ook is 18F-FDG biodistribusie na IFI/IF en tumors soortgelyk en dit veroorsaak 'n beperking op die vermoë om te onderskei tussen hierdie spesifieke siektetoestande. In die soektog na die ideale radiofarmaseutiese middel vir tumor/IFI/IF deteksie, het die South African Nuclear Energy Corporation (Necsa) twee verskillende merkingsroetes van etileendisisteien-deoksiglukose (EC-DG) met 99mTc ontwikkel, wat plaaslik voorberei kon word by die Departement Kerngeneeskunde by die Universitas Akademiese Hospitaal. Die samevoeging van verskillende siektes en fisiologiese toestande wat by mense voorkom kan gesimuleer word deur die gebruik van modeldiere vir navorsing. Drie verskillende spesies diere is gebruik om die nodige navorsingsdata te verkry wat bygedra het tot die evaluering van die diagnostiese potensiaal van die IHP 99mTc-EC-DG. Al drie spesies diere het verhoogde biodistribusie van die IHP 99mTc-EC-DG na die lewer (kritiese orgaan) en hart gehad. IHP 99mTc-ECDG is vinnig opgeklaar deur die niere, wat waargeneem is as 'n afname in agtergrondaktiwiteit in diere op die sintigrafiese beelde. Die IHP 99Tc-EC-DG beelde het geen biodistribusie na die brein gewys in die groter modeldiere nie. Dit is die grootste verskil in die biodistribusie van IHP 99mTc-EC-DG wanneer vergelyk word (met literatuur) met kliniese 18F-FDG studies wat hoë opname in die brein toon. Die gevolgtrekking kan gemaak word dat die IHP 99mTc-EC-DG nie deur die bloed brein skans (BBS) kan beweeg nie, in ooreenstemming met vroeëre bevindings in die literatuur. Die IHP 99mTc-EC-DG het soortgelyke opname as 18F-FDG in longtumors, wat geïnduseer is in naakte muise, getoon. Daar is ooreenkomste tussen die opname van IHP 99mTc-EC-DG en 99mTc-EC-DG beskryf in die literatuur deur Yang et al. (2003:470-471). Dit sluit die biodistribusie na longtumors, biodistribusie na die lewer en hart en ekskresie deur die niere in. IHP 99mTc-EC-DG opname in septiese (Escherichia coli) en steriele (zymosan) IFI/IF wat geïnduseer is in Nieu-Seeland wit konyne, is geëvalueer en vergelyk met 67Ga-sitraat opname. IHP 99mTc-EC-DG is afhanklik van 'n sellulêre respons en gebruik hoofsaaklik hierdie meganisme vir opname in IFI/IF, terwyl 67Ga-sitraat verskeie meganismes vir opname het. IHP 99mTc-EC-DG word opgeneem in laegraadse sellulêre IFI/IF. Vroeë diagnose van laegraadse (zymosan) en bakteriële IFI/IF is moontlik met IHP 99mTc-EC-DG. Die IHP 99mTc-EC-DG kan 'n veel goedkoper en meer bekostigbare diagnostiese alternatief wees as 18F-FDG en 67Ga-sitraat vir tumor en IFI/IF beelding. Uit die navorsing gedek in hierdie tesis is daar geen twyfel dat die IHP 99mTc-EC-DG belowende deteksie karakteristieke vir beide IFI/IF en spesifieke tumors het nie en dus is menslike kliniese proewe geregverdig. Verder het IHP 99mTc-EC-DG toekomstige potensiaal om diagnose en prognose te verbeter en beplanning en monitering van kankerbehandeling in mense moet verder ondersoek word.af
dc.language.isoenen_ZA
dc.publisherUniversity of the Free Stateen_ZA
dc.subjectIn-house prepared 99mTc-EC-DGen_ZA
dc.subjectBiodistributionen_ZA
dc.subjectInfection/ inflammationen_ZA
dc.subjectTumouren_ZA
dc.subjectImagingen_ZA
dc.subjectAnimal models in researchen_ZA
dc.subjectDisease -- Animal modelsen_ZA
dc.subjectThesis (Ph.D. (Clinical Nuclear Medicine))--University of the Free State, 2015en_ZA
dc.titleIn-house prepared 99mTc-ethylenedicysteinedeoxyglucose in mice, rabbits and baboons: tumour, local infection/inflammation and normal biodistributionen_ZA
dc.typeThesisen_ZA
dc.rights.holderUniversity of the Free Stateen_ZA


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