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Item Open Access The value of Technetium-99-Metastable-Ethylenedicysteine-eoxyglucose (⁹⁹ᴹTC-EC-DG) imaging in patients with Rheumatoid Arthritis(University of the Free State, 2023) Evbuomwan, Osayande; Horn-Lodewyk, Je'nine; Labuschagne, Mathys J.; Driver, Cathryn H. S.Rheumatoid arthritis (RA) is a systemic inflammatory disease that is usually associated with synovitis that can lead to progressive joint damage if not managed appropriately. Prompt diagnosis and early treatment offer a good prognosis in patients with RA. However, treatment monitoring remains challenging for the rheumatologist as it is sometimes difficult to differentiate true remission from subclinical disease. Several modalities are available for assessing disease activity in patients with RA. This usually involves a combination of the clinical assessment of involved joints, laboratory and imaging investigations. Imaging with ultrasound (US) and magnetic resonance imaging (MRI) are considered to be among the most sensitive methods of assessing disease activity. However, these modalities are not without shortcomings. The aim of this study was to investigate the use of technetium-99-metastable ethylenedicysteine-deoxyglucose (⁹⁹ ͫ Tc-EC-DG) in the management of patients with RA. Using ⁹⁹ ͫ Tc-EC-DG to identify synovitis and offer prognostic information was investigated. Its usefulness in assessing treatment response compared to US and the diagnostic accuracy of identifying the disease compared to US was also investigated. A prospective study was conducted at the Department of Nuclear Medicine of the University of the Free State/Universitas Academic Hospital in Bloemfontein, South Africa. Twenty-two participants seen at the Rheumatology Unit of the Department on Internal Medicine, diagnosed with RA, were enrolled according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria. Participants were injected with 20–25 millicurie (mCi) of ⁹⁹ ͫ Tc-EC-DG. Flow, blood pool, whole body, delayed static, and SPECT/CT images were acquired. Known disease sites were qualitatively assessed for the intensity of uptake, and disease severity was graded (Grade 0–3). On the same day, US imaging of the most affected joints was performed in addition to blood samples being obtained from each participant for baseline C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody titre. All imaging and laboratory investigations were performed at baseline, six weeks and six months follow-up after baseline findings in 20 of the participants. The median (interquartile range) age was 59 (49–68) years, and the majority (n=21; 95.5%) of patients were female. An abnormally increased uptake of ⁹⁹ ͫ Tc-EC-DG was noted in the majority of the sites of known disease, including unknown sites. SPECT/CT imaging localised tracer uptake specifically to the synovial space. Fourteen (63.6%) of the 22 participants had elevated RF and anti-CCP antibody titres. A significant correlation between higher grade uptake and increased levels of RF and anti-CCP antibodies (p=0.031) was observed. A total of 404 joints were evaluated by ⁹⁹ ͫ Tc-EC-DG and US imaging. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of ⁹⁹ ͫ Tc-EC-DG SPECT/CT imaging were 86%, 60%, 61%, 85% and 73%, respectively, using US as the gold standard. A sensitivity of 100% was noted in the identification of synovitis in the carpal and knee joints. Disease activity in the distal interphalangeal (DIP) joints was not observed with either ⁹⁹ ͫ Tc-EC-DG or US imaging. The level of agreement between US and ⁹⁹ ͫ Tc-EC-DG imaging in assessing therapy response was 33.3 %, 11.6 % and 6.67 % for the knees, hands and wrist joints, respectively. ⁹⁹ ͫ Tc-EC-DG is a safe radiopharmaceutical that can effectively assess disease activity in the joints of patients with RA, with a strong correlation between high-grade disease on imaging and the presence of RF and anti-CCP antibodies. It has a high sensitivity in detecting synovitis when compared to US imaging. However, it has a poor correlation in the assessment of treatment response in comparison to US findings, which might be attributed to its ability to better detect subclinical disease. Using ⁹⁹ ͫ Tc-EC-DG offers facilities with only SPECT or SPECT/CT cameras an opportunity to investigate patients with RA.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. ___________________________________________________________________