Nuclear Medicine

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99mTc-MIBI stress-rest myocardial perfusion scintigraphy in patients with complete left bundle branch block
(2001) Ellmann, A.; Van Heerden, P. D. R.; Van Heerden, B. B.; Klopper, J. F.
Background. Patients with complete left bundle branch block (LBBB) often show a false-positive ischaemic pattern in the interventricular septum on thallium-201 (201Tl) stress-rest myocardial perfusion scintigraphy. Equivocal results have been reported with technetium-99m labelled hexakis-methoxyisobutyl isonitrile (99mTc-MIBI) in such patients. The aim of this retrospective study was to determine the effect of LBBB on the septal uptake of 99mTc-MIBI during stress-rest single photon emission computed tomography (SPECT) scintigraphy. Methods. We studied 75 consecutive patients with LBBB, referred for 99mTc-MIBI stress-rest SPECT. Studies were evaluated by visual analysis using a semi-quantitative grading technique. In all patients with abnormal septal segments, the presence or absence of ischaemic heart disease was confirmed either clinically or by means of angiographical examination. Results. Forty-three patients (57.3%) had completely normal studies. Only 15 (20%) had septal abnormalities (11 with reversible and 4 with fixed defects), while 17 patients (22.7%) had abnormal segments in areas other than the interventricular septum. Except for 1 patient lost to follow-up, ischaemic heart disease was confirmed in all the patients with septal changes. Conclusion. We conclude that 99mTc-MIBI is more specific than 201Tl for identifying ischaemic heart disease in the presence of LBBB.
The added value of SPECT/CT in complicated osteomyelitis
(Stellenbosch : Stellenbosch University, 2013-12) Tag, Naima; Korowlay, Nisaar A.
ENGLISH ABSTRACT: Background: The detection of bone infection can be very difficult especially in bone with altered structure due to prior trauma or surgical procedures. Complicated osteomyelitis (COM) is becoming a public health problem especially with the difficult choice between, high cost surgery and prolonged courses of intravenous or oral antibiotic therapy, as well as the social and psychological effect of longterm disease and disability of the patient. The correct localisation of especially bone infection is still a challenge for the clinician. The single photon emission computed tomography/low dose computed tomography (SPECT/CT), by fusing the functional information with the anatomical parts, is a wellestablished tool used in many nuclear medicine studies. This improves the overall quality of the study with more clear answers. The aim of the study was to determine the added value of SPECT/CT in the management of complicated osteomyelitis (COM) in patients with endo-prosthesis, post traumatic osteomyelitis with and without metal implants and diabetic foot. Methods: This was a prospective study, between February 2010 and February 2012. Patients with suspected COM who fulfilled the selection and inclusion criteria were included. All had abnormal three phase bone scan followed by infection imaging with 99mTc labelled white blood cells and 99mTc -colloid if the99mTc labelled white blood cell study was abnormal. 67Ga citrate was used in vertebral involvement. Planar and SPECT/CT images were reviewed for presence of abnormal uptake and for its localization in bone and soft tissue. Scan results were defined as positive or negative. Both planar and SPECT/CT images were compared regarding diagnosis and precise localization of infection. The final diagnosis was obtained from surgical specimen or microbiological culture as well as clinical follow-up of all patients. Results: There were 72 patients, 29 male and 43 female with mean age of 57 yrs [range 27-88].There were 24 patients with prosthesis, 16 with hip prosthesis (PH=16), and 8 with knee prosthesis (PK=8). There were 44 patients with post traumatic osteomyelitis, 26 with metal implants (TOM=26) and 18 without metal implants (TOWM= 18). Four patients had diabetic foot (DF= 4). Infection was diagnosed in 19/72 patients on planar images and in 21/72 on SPECT/CT. Infection was diagnosed in 4 patients with prosthesis, 16 patients with post traumatic injury and one diabetic foot patient. The four patients with prosthesis, SPECT /CT added diagnostic value by excluding osteomyelitis in 3 patients and by defining the exact extent and localizing soft tissue and bone infection (STI/OM) in one patient. In 16 patients with post traumatic OM on planar images, SPECT /CT added diagnostic value, by excluding OM in 4 patients and confirming only STI, better localisation of the uptake in bone and soft tissue in 5 patients, of them 2 patient was negative on planar, and in 7 patients, confirmed and defined the exact extent of both OM and STI. One diabetic foot was positive for STI on the planar, the SPECT/CT added diagnostic value by defining the extent of the infection. In summary the added value of SPECT/CT was: a. Overall infection: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (10%) 2. Better localization in bone and soft tissue: 6 patients (8%) 3. Better delineation of extent of infection: 9 patients (12%) 4. None: 50 patients (70%) b. In positive cases only: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (33%) 2. Better localization in bone and soft tissue: 5 patients (24%) 3. Better delineation of extent of infection: 9 patients (43%) 4. None: 0 patients The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy for infection, on planar was 90%, 100%, 100%, 97%, 97%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. For OM on planar, the sensitivity, specificity , positive predictive value, negative predictive value and accuracy was 100%, 89%, 53%, 100%, 90%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. Conclusion: In complicated osteomyelitis, SPECT/CT is useful in localizing, defining the exact extent of infection where the planar images are abnormal, with no added value if the planar images are negative. We recommend in clinical practice the routine use of hybrid SPECT/CT imaging in complicated osteomyelitis when planar images are abnormal.
The added value of SPECT/CT in the evaluation of equivocal skeletal lesions in patients with known malignant disease
(Stellenbosch : University of Stellenbosch, 2010-03) Ndlovu, Xolani; Warwick, James M.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH SUMMARY: Introduction: Bone scintigraphy is used extensively in evaluating metastatic disease. There are currently no clear recommendations for the use of SPECT/CT in metastatic bone disease. Existing procedural guidelines from the Society of Nuclear Medicine (SNM) for SPECT/CT do not provide specific indications for use of SPECT/CT in bone scintigraphy, and there are currently no other guidelines for the use of SPECT/CT in bone scintigraphy that the author is aware of. The aim of this study was to investigate the additional value of SPECT/CT, and to identify the clinical indications for which SPECT/CT is most useful in patients with suspected bone metastases. Subjects and Methods: Forty-two patients with equivocal lesions on planar scintigraphy were prospectively recruited and planar imaging, SPECT, and SPECT/CT done on all patients. On reading of SPECT and then SPECT/CT, patients and individual lesions were classified as malignant, benign or equivocal. Radiological studies and available clinical information were also used during reading of scans. Review of clinical information, radiological studies and/or follow-up bone scans were used as gold standard. The results of the SPECT and SPECT/CT were compared in terms of proportion of equivocal findings and accuracy. Results: Forty-two patients with 189 skeletal lesions were examined. There was a diverse variety of primary tumours, although the majority had breast (n=22) or prostate cancer (n=8). Overall, SPECT/CT resulted in a significant reduction in the proportion of equivocal findings on both a patient-wise (p=0.0015) and lesion-wise basis (p<0.0001). The overall accuracy of SPECT/CT was significantly higher than that of SPECT on both a patient-wise (p=0.0026) and lesion-wise basis (p<0.0001). Generally SPECT/CT decreased the proportion of equivocal findings and increased the accuracy independent of the presence of bone pain, type of primary tumour, or skeletal region involved. SPECT/CT did not significantly improve the diagnostic confidence of readers in equivocal lumbar lesions although accuracy was significantly improved in this region. Conclusion: SPECT/CT performs significantly better than SPECT alone for the interpretation of equivocal planar lesions. There is no evidence that the benefit of SPECT/CT is dependent on the type of primary tumour or the presence of bone pain. Where resources are limited, SPECT/CT is indicated only in those patients in whom correct classification of the lesions in question is expected to alter the patient’s management. SPECT/CT images should be interpreted with the aid of a diagnostic radiologist or nuclear medicine physicians should acquire sufficient experience in Computed Tomographic image interpretation in order to optimise diagnostic benefit from SPECT/CT.
Appropriate indications for positron emission tomography/computed tomography : College of Nuclear Physicians of the Colleges of Medicine of South Africa
(Health & Medical Publishing Group, 2016) Sathekge, Mike; Warwick, James M.; Doruyter, Alex; Vorster, Mariza
Individualised patient treatment approaches demand precise determination of initial disease extent combined with early, accurate assessment of response to treatment, which is made possible by positron emission tomography/computed tomography (PET/CT). PET is a non-invasive tool that provides tomographic images and quantitative parameters of perfusion, cell viability, and proliferation and/or metabolic activity of tissues. Fusion of the functional information with the morphological detail provided by CT as PET/CT can provide clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Three large-scale national studies published by the National Oncologic PET Registry in the USA have shown that imaging with PET changes the intended patient management strategy in 36.5% to 49% of cases, with consistent results across all cancer types. The proven clinical effectiveness and growing importance of PET/CT have prompted the College of Nuclear Physicians of South Africa, in collaboration with university hospitals, to develop a list of recommendations on the appropriate use of fluorine-18-fluorodeoxyglucose (18F-FDG) and non-18F-FDG PET/CT in oncology, cardiology, neurology and infection/inflammation. It is expected that other clinical situations will be added to these recommendations, provided that they are based upon solid clinical evidence. These recommendations are intended to offer advice regarding contemporary applications of PET/CT, as well as indicating novel developments and potential future indications. The CNP believes that these recommendations will serve an important and relevant role in advising referring physicians on the appropriate use of 18F-FDG and non-18F-FDG PET/CT. More promising clinical applications will be possible in the future, as newer PET tracers become more readily available.
Brain SPECT in patients with neuropsychiatric SLE : the additional value of semi-quantitative analysis
(Stellenbosch : University Stellenbosch, 2009-12) Khider, Mohamed Abdelrahman; Warwick, James; Whitelaw, Dave; University of Stellenbosch. Faculty of Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH ABSTRACT: Introduction: There is conflicting data on the value of single photon emission tomography (SPECT) for the diagnosis of neuropsychiatric SLE (NPSLE). Visual assessment of brain SPECT scans is the standard approach in clinical practice. However the definition and identification of significant changes may be limited by a high interobserver variability, especially in centres with limited experience. This may be reduced by a more objective semi-quantitative assessment. The objectives of this study were to determine the sensitivity and specificity of SPECT for the detection of NPSLE at our institution using visual assesment, to determine the additional value of using an objective semi-quantitative diagnostic criterion, and to investigate the correlation between abnormal perfusion pattern and clinical NPSLE classification in patients with active NPSLE. Material and methods: Nineteen patients with NPSLE and 19 normal controls were studied with brain SPECT. Scans were interpreted blindly by two nuclear medicine physicians using two methods; visual and semi-quantitative assessments. In the visual method, overall visual impression was recorded for each scan using a four point scale, where A=normal, B=probably normal, C=probably abnormal, and D=abnormal. In addition, each brain region was assigned a severity score from 0=normal perfusion to 3=severe hypoperfusion. In the semi-quantitative assessment, ten-band color scale was used, and perfusion deficit was quantified on the side with the lower color intensity comparing to the contralateral side. A score was given to the region with perfusion deficit according to the difference (in color bands) between the two hemispheres. Analysis was performed for the visual assessment method (overall impression and severity scores) and the semi-quantitative assessment method using a receiver operator characteristic (ROC) curve. Optimal cut-off points were determined and the accuracy of the different techniques was also compared statistically. Finally, the correlation was determined between the SPECT perfusion pattern and the clinical pattern of disease. Results: An ROC curve analysis for the overall visual impression resulted in an area under the curve of 0.76. At a cut-off point of C (probably abnormal), brain SPECT had 89% sensitivity and 57% specificity for the diagnosis of NPSLE. The severity score which include the total severity score and the modified total severity score resulted in areas under the curve of 0.75 and 0.79 respectively. The semi-quantitative assessment resulted in areas under the ROC curve of 0.80. Statistically, there was no difference between the overall visual impression, visual severity scores, and the semi-quantitative assessment. Agreement analysis between the SPECT pattern and clinical pattern of disease showed agreement in 91.6% in the diffuse pattern, whereas agreement in the focal pattern was seen in only 42.8%. Discussion and Conclusion: In this study, we found that brain SPECT is able to diagnose active NPSLE with a high sensitivity and moderate specificity. The overall visual impression, visual severity scores, and the semi-quantitative assessment showed no significant differences between the techniques. The use of the semi-quantitative assessment described may be useful in centers with limited experience in the interpretation of brain SPECT. The correlation between the SPECT pattern and clinical disease pattern may provide some insights into the pathophysiology of NPSLE.
A case for the provision of positron emission tomography (PET) in South African public hospitals
(Health and Medical Publishing Group, 2006-07) Sathekge, M. M.; Warwick, James M.; Vangu, M. D. T.; Ellmann, A.; Mann, M.
Nuclear medicine is expanding into new areas of clinical practice, of which positron emission tomography (PET) is an example. As in new treatments with labelled monoclonal antibodies, especially for lymphoma, the wide introduction of PET into health care in South Africa presents benefits and challenges to patients, doctors, and funders. PET is an imaging modality that has been available in specialised centres in the developed world since the 1970s. It was initially used as a research tool to image organ function in vivo. The development of the radiopharmaceutical F-18- fluorodeoxyglucose (FDG), a glucose analogue taken up avidly by the majority of tumours, has resulted in PET now being used routinely in the management of many cancer patients in centres with access to it. There has been rapid growth of PET in the developed world and it has also been introduced into developing countries, including Egypt. We welcome government initiatives to establish PET imaging in South Africa, as evidenced by the provision of cyclotrons in Gauteng and Cape Town.
The College of Nuclear Physicians of South Africa practice guidelines on peptide receptor radionuclide therapy in neuroendocrine tumours
(Health and Medical Publishing Group, 2018) Lawal, I.; Louw, L.; Warwick, James M.; Nyakale, N.; Steyn, R.; Lengana, T.; Ellmann, A.; Kotze, T; Vangu, M.; Vorster, M.; Sathekge, M.
Background: Peptide receptor radionuclide therapy (PRRT) for metastatic or inoperable neuroendocrine tumours (NETs) is a systemic therapy which targets somatostatin receptors overexpressed by differentiated NETs for endoradiotherapy. This guideline has been compiled by the College of Nuclear Physicians of the Colleges of Medicine of South Africa, with endorsement by the South African Society of Nuclear Medicine and the Association of Nuclear Physicians to guide Nuclear Medicine Physicians in its application during the management of these patients. Recommendations: Patients with well- to moderately-differentiated NETs should be comprehensively worked-up to determine their suitability for PRRT. Treatment should be administered by a Nuclear Medicine Physician in a licensed, appropriately equipped and fully staffed facility. Patient monitoring is mandatory during and after each therapy cycle to identify and treat therapy-related adverse events. Patients should also be followed-up after completion of therapy cycles for monitoring of long-term toxicities and response assessment. Conclusion: PRRT is a safe and effective therapy option in patients with differentiated NETs. Its use in appropriate patients is associated with a survival benefit.
Dual energy window imaging for optimisation of P/V ratios in VP SPECT
(SpringerOpen, 2021) Doruyter, Alex G. G.; Holness, J. L.
Purpose: Ventilation–perfusion single-photon emission computed tomography (VP SPECT) plays an important role in pulmonary embolism diagnosis. Rapid results may be obtained using same-day ventilation followed by perfusion imaging, but generally requires careful attention to achieving an optimal count rate ratio (P/V ratio) of ≥ 3:1. This study investigated whether the ratio of counts simultaneously acquired in adjacent primary and Compton scatter energy windows (Eratio) on V SPECT was predictive of final normalised perfusion count rate ( PCRnorm) on P SPECT using [ 99mTc]Tc-macroaggregated albumin (MAA), thus allowing for optimisation of P/V ratios. Methods: Same-day VP SPECT studies acquired using standard protocols in adult patients during a 2-year period (training dataset) were assessed. Studies were included provided they were acquired with correct imaging parameters, and injection site imaging and laboratory records were available for quality control and normalised count rate corrections. Extraction of DICOM information, and linear regression were performed using custom Python and R scripts. A predictive tool was developed in Microsoft Excel. This tool was then validated using a second (validation) dataset of same-day studies acquired over a subsequent 7-month period. Accuracy of the prediction tool was assessed by calculating the mean absolute percentage error (MAPE). Results: Of 643 studies performed, the scans of 342 participants (median age 30.4 years, 318 female) were included in the training dataset, the analysis of which yielded a significant regression equation (F(1,340) = 1057.3, p < 0.0001), with an adjusted R2 of 0.756 and MSE of 0.001089. A prediction tool designed for routine clinical use was developed for predicting final P/V ratio. Of an additional 285 studies, 198 were included in the second (validation) dataset (median age 29.7 years, 188 female). The Excel-based tool was shown to be 91% accurate (MAPE: 9%) in predicting P/V ratio. Conclusion: The relationship between the ratio of simultaneously acquired counts in adjacent energy windows on V SPECT and perfusion count rate after administration of a known activity of [ 99mTc]Tc-MAA can be linearly approximated. A predictive tool based on this work may assist in optimising the dose and timing of [ 99mTc]Tc-MAA administration in same-day studies to the benefit of patients and workflows.
The effect of reconstruction algorithms (iterative versus filtered backprojection) on the diagnosis of single pulmonary nodules using Thallium-201 and Technetium-99m MIBI SPECT
(Stellenbosch : Stellenbosch University, 2004-04) Ambayi, Rudo; Ghoorun, S.; Dupont, P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH ABSTRACT: This study involved 33 patients, 19 men and 14 women. The age range was wide (20-90 years) and median age was 57 years. These patients had a single pulmonary nodule (SPN) defined radiologically as a well defined, round or oval intrapulmonary lung lesion not associated with atelectasis or adenopathy on chest radiography or computed tomography. Patients were investigated with Tc-99m MIBI and TI-201 (25 patients) and with Tc-99m MIBI alone (8 patients). Single photon emission computed tomography images were reconstructed using both iterative reconstruction (Ordered Subsets - Expectation Maximisation: aSEM) and filtered backprojection (FBP), on the Hermes system. Transverse, coronal and sagittal slices were displayed on the screen using a grey scale. The aSEM and FBP images for each study were co-registered semi-automatically using the multimodality programme on the Hermes. The best slice for the lesion was chosen according to the best view used to locate the SPN on chest radiograph. Regions of interest (Ral) were drawn manually outside the outer margin of the detected lesion, first on the aSEM image. This was automatically mirrored on the co-registered FBP image. For most patients, the background was automatically mirrored horizontally on the contralateral side, again, first on the OSEM then automatically on the FBP image. Automatic vertical mirroring or manual horizontal mirroring was used when background was found to be in a visually 'hot' area like the heart or vertebrae. The average counts and standard deviation of the Ral and background were generated automatically. Semi-quantitative image analysis was done by calculating the signal-to-noise ratio (SNR) and tumour-to-background (TIB) ratio using the following formulae: SNR = Mean counts ROI(lesion) - Mean counts background Standard deviation background TIB rati.o = -M---e-a-n-'--c-o--u-n-'t-s- ROI(lesion) Mean counts background Detection was found to be the same for the two reconstruction algorithms, that is, every lesion detected by using OSEM could also be detected by using FBP. However lesion detection did differ between Tl-201 and Tc-99m-MIBI. Sensitivity and specificity were calculated for different thresholds of SNR and TIB ratios. Receiver operating characteristics (ROC) curves were drawn to represent the different sensitivities and specificities at each threshold. Tuberculosis (TB) was not included in this analysis as uptake of Tl-20l was found to be significantly high and comparable to that of malignant nodules. However the effect of OSEM and FBP on the 'positive' TB nodules was assessed separately. By calculating the area under the ROC curves, TI-201 using OSEM was shown to be more accurate at differentiating malignant nodules from benign ones than FBP. Although this difference was not statistically significant (p=0.1 0), there was a clear tendency. The two reconstruction algorithms were found to be almost equally accurate, when using Tc-99m-MIBI, the difference between them being considerably insignificant. In conclusion, it was shown that there is a tendency that OSEM outperforms FBP for studies using Tl-201 but not for Tc-99m-MIBI.
The elimination of errors caused by prior technetium-99m scintigraphy on iodine-131 thyroid uptake measurements.
(Health & Medical Publishing Group, 1987) Wasserman, H. J.; Muller, C.; Klopper, J. F.
Coincidence summing of technetium-99m (99mTc) pulses may disturb iodine-131 (131I) thyroid uptake measurements if these are obtained after 99mTc thyroid scintigraphy performed on the same day. The magnitude of the error was assessed in 26 patients. It was found that when pre-dose measurements were subtracted, the 6-hour and 24-hour 131I uptakes could be falsely decreased by up to 137 percentage points using a lower discriminator level of 250 keV and by up to 35 percentage points with a discriminator level of 300 keV. When pre-dose measurements from 99mTc were ignored, there was a general increase in 131I uptake values at 6 hours. Increases of up to 22 and 9 percentage points occurred when 250 keV and 300 keV lower discriminator levels respectively were used. These errors may be eliminated by performing 131I uptake measurements through a 1 mm lead filter.
Evaluation of BCL-2 and PARP-1 as potential therapeutic targets to radiosensitise lung cancer
(Stellenbosch : Stellenbosch University, 2021-12) Guillaume, Muteba Mpolesha; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH SUMMARY : Lung cancer remains the most incident malignancy worldwide, representing 13% of all cancers. It is also the leading cause of death in the world, accounting for 18 18.2% of global cancer-related deaths. The burden of lung cancer in Africa is increasing due to ag ageing an and population growth, increased prevalence of risks factors such as smoking, occupational exposure, infections, lifestyle changes, and environmental pollutants. The efficacy of many therapeutic strategies has been hindered by normal tissue toxicity and treatment resistance. For many cancer patients, radiotherapy has been the chosen therapeutic option to minimise cancer cell spread by shrinking the tumour while ensuring protection of normal tissue. There is evidence that small molecule inhibitor s can effectively target cell survival signa signalling pathways, but cancer cell cells manage to find molecular escape routes to either repair the damage or evade cell death. Combination therapy appears to be an appropriate approach to address these challenges. Therefore, targeting more than one component of the cell survival signa signalling pathways could potentially sensitise cancer cells to irradiation and improve the outcome of radiotherapy. The purpose of this study was to evaluate the role of targeting the anti-apoptotic (B-cell lymphoma 2 (Bcl -2)) pathway and the DNA repair (poly (ADP ADP-ribose) polymerase 1 (PARPPARP-1)) pathway with specific inhibitors in modulating the radiosensitivity of a lung cancer cell line ( and an apparently normal lung cell line ( For this, Bcl -2 and PARP PARP-1 were inhibited using ABT ABT-737 and ABT ABT-888, respectively. At a dose of 2 Gy, the typical fractional dose in conventional radiotherapy, combined inhibition of Bcl-2 and PARP-1 or inhibition of Bcl-2 alone resulted in significant radio-sensitisation in only the A549 cells. However, at a larger radiation dose of 6 Gy (a potentially useful fractional dose in hypo-fractionated radiotherapy), inhibition of Bcl-2 and PARP-1 markedly radio-sensitised the apparently normal (L132) and malignant (A549) cell lines, respectively. These findings suggest that use of Bcl-2 and PARP-1 inhibitors might be beneficial when combined with conventional radiotherapy, but not with hypo-fractionated radiotherapy when large fractional radiation doses are employed. However, validation of these results with a larger panel of cell lines is warranted.
Evaluation of small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 for their radiomodulatory effects in human breast cancer cell lines
(Stellenbosch : Stellenbosch University, 2016-12) Hamunyela, Roswita Hambeleleni; Akudugu, John M.; Serafin, Antonio Mendes; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH SUMMARY : Breast cancer remains the most commonly diagnosed cancer in women. It is responsible for 32% of all cancers and 15% of all cancer-related deaths in females. Patients with triple-negative breast cancers (TNBC) constitute about one-fifth of all breast cancer patients. TNBC is an aggressive and heterogeneous disease entity in comparison with other types of breast cancer and, therefore, tends to be resistant to existing treatment regimens, such as, targeted and hormone therapies. Although cancer treatment has evolved from being invasive and highly toxic to being more specific with reduced normal tissue toxicity, intrinsic tumor resistance still limits the benefit of therapy with radiation, drugs, and antibodies. To address this important clinical challenge, attempts have been made to better understand the molecular determinants of treatment resistance. This resistance can be attributed to the heterogeneity in the distribution of potential target antigens in a given tumor cell population, which leads to the inability to effectively target all cells with toxic levels of a particular therapeutic agent. There is evidence to suggest that proliferative pathways of triple-negative tumors are still poorly understood, which could be the reason for the observed treatment resistance. Targeted treatment modalities that are singly effective for triple-negative breast cancer are lacking, partly due to paucity of relevant targets as they are devoid of the human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and oestrogen receptor (ER). Novel treatment approaches are, therefore, needed to overcome the challenges in the treatment of triple-negative breast cancers if treatment outcomes are to be improved. Concomitant targeting of cell signaling entities other than HER2, PR and ER may sensitize triple-negative tumors to radiotherapy. In this study, inhibition of HER2, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and the pro-survival gene (Bcl-2) with small molecule inhibitors, TAK-165 (against HER2), NVP-BEZ235 (against PI3K and mTOR), and ABT-263 (against Bcl-2), singly or as cocktails, resulted in significant radio sensitization of human breast cell lines with features similar to those of triple negative cancers. This radio sensitization was seen at 2 and 6 Gy, indicating that a therapeutic benefit could be derived in conventional as well as stereotactic radiotherapy. A moderate to strong synergism was also demonstrated for NVPBEZ235/TAK-165 and NVP-BEZ235/ABT-263 cocktails. The strongest synergy was seen in the latter cocktail. In conclusion, inhibition of PI3K, mTOR and Bcl-2 could potentially be effective in the treatment of triple-negative breast cancer. The therapeutic benefit can be improved, if the target inhibition is followed by radiotherapy.
Evaluation of the effect of low and intermediate frequency electromagnetic waves on radiosensitivity
(Stellenbosch : Stellenbosch University, 2016-12) Chinhengo, Angela; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH SUMMARY : The incidence of epidemic Kaposi’s sarcoma in HIV/AIDS patients is high due to their compromised immune system. HIV-positive individuals presenting with cancer tend to be more sensitive to ionizing radiation and are at a higher risk of developing severe side effects during radiotherapy, and there is a need to develop non-invasive methods to preferentially sensitize cancer cells and reduce therapeutic doses. Here, the effects of 100 and 1000 Hz electromagnetic fields (EMF) broadcast via an argon plasma ray tube at 50 W on the radio sensitivity of apparently normal Chinese hamster lung fibroblasts (V79) and human malignant melanoma cells (MeWo) were evaluated using the colony forming assay. Pre-exposure of the fibroblasts to both fields had no effect on their radio sensitivity, if X-ray irradiation followed within 2 h or at 6 h. Significant radio sensitization was observed when X-rays were administered 4 h after EMF exposure. For the MeWo cells, pre-exposure to 100 Hz resulted in a significant radioprotection when irradiation followed within 6 h. However, treatment of these cells with a 1000 Hz field significantly potentiated the effect of X-rays. When cells were irradiated prior to EMF exposure, the V79 cells were marginally protected by the 100 Hz field and sensitized by the 1000 Hz field. In contrast, the melanoma cells were slightly protected by the 1000 Hz field and sensitized by the 100 Hz field. The survival rate of the normal fibroblasts when treated with 2 Gy, in two fractions of 1 Gy 6 h apart, was similar to those obtained when cells received an acute dose of 2 Gy 6 h prior to or after exposure to both EMF frequencies. On the other hand, the melanoma cells were significantly sensitized when they were either treated with a combination of X-rays and then 100 Hz EMF 6 h later or with a combination of either of the EMF frequencies and then X-rays 6 h later. These data suggest that use of electromagnetic fields may sensitize tumours to radiation therapy and reduce normal tissue toxicity. Informed and well-designed combinations of low-medium frequency electromagnetic fields and radiation therapy might be beneficial in the management of cancers, especially epidemic Kaposi’s sarcoma.
Extended Cr-51 RBC combined with Tc-99m RBC for the detection and localisation of occult GIT bleeding
(Stellenbosch : Stellenbosch University, 2014-04) Modebe, Emmanuel Obinna; Ellmann, Annare; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology, Nuclear Medicine. Radiodiagnosis.
ENGLISH ABSTRACT: Background Occult blood loss from the gastrointestinal tract (GIT), causing iron deficiency often with anaemia, can be diagnostically and therapeutically challenging. This is because the endoscopic and radiologic tests may be negative due to the slow, chronic and intermittent nature of the gastrointestinal bleeding, making timing key in detection and localisation of the bleed. These limitations can be approached using two different radioactive isotopes. Firstly, we tested the sensitivity of extending Cr-51 RBC for 21 days relative to 5 days to detect GIT bleeding and its use to optimise timing of a Tc-99m RBC study for GIT blood loss localisation. Finally, we tested if the information provided by the Tc-99m RBC study aided gastroenterologic intervention for anatomical localisation of a lesion. Method In this retrospective review, after obtaining institutional and ethics committee approval, records of patients referred for evaluation of possible GIT blood loss were reviewed. In each; daily appearance of radiochromium in stool was measured in the whole body counter. In those cases exceeding 50 ml/day, a technetium-99m (Tc-99m) localization study was performed. These studies were correlated with clinical findings. Results A total of 59 Cr-51 RBC studies were carried out in 36 females and 21 males (n = 57). In 32 (54%) the radiochromium results were positive with 75% of the bleeding incidences occurring after 5 days of stool collection. Of 17 cases in whom Tc-99m RBC imaging studies were performed, 14 (82%) were positive with specific anatomical sites successfully defined in twelve. In all patients with blood loss of >100 ml/24h, Tc-99m RBC were positive and localised. Ten of the 17 Tc-99m RBC studies were further investigated and half diagnosed with small-bowel angiodysplasia. Conclusion This sequential twin isotope method is practical in revealing otherwise silent intestinal haemorrhage. Although it has good patient acceptability and clinical as well as diagnostic utility in management, further studies are required to clearly establish a cut-off level of blood loss for performing imaging studies and the impact of the findings on the overall patient management.
First-pass determination of the right ventricular ejection fraction using two regions of interest and the right anterior oblique view
(HMPG, 1984) Wasserman, H. J.; Otto, A.
The right ventricular ejection fraction (RVEF) was determined on the right anterior oblique view in 9 patients during the first pass of a bolus of technetium-99m employing a gamma camera with high count-rate capability. The RVEF was calculated by using: (i) a fixed end-diastolic region of interest (ROI); and (ii) an end-diastolic and end-systolic ROI. Because of the movement of the tricuspid plane the first of these methods often gave low values, and agreement between the first two peaks was not as good as that when the second method was used. The mean for the second method was in agreement with that in a previous study using a gated first pass technique and two ROIs but was somewhat higher than those reported by workers using either one ROI or the anterior view.
Glomerular filtration rate measurement and estimation : improvement and validation of existing methods
(Stellenbosch : Stellenbosch University, 2019-12) Holness, Jennifer Lyn; Warwick, James Mathew; Davids, Mogamat Razeen; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH SUMMARY : Glomerular filtration rate (GFR) is regarded as the best measure of kidney function. It can either be measured or estimated. This dissertation aims to provide a better understanding of GFR measurement in order to improve its performance and interpretation. It also aims to validate GFR estimation in local populations and to demonstrate the utility of simple adaptations of existing equations to improve estimation. On completion of a GFR measurement, various quality control (QC) checks are performed to ensure the accuracy of the result. However, this requires comparison with clearly defined reference ranges. In a study of healthy, potential kidney donors, reference data for two QC parameters were defined. In a study analysing the effect of measurement errors on GFR, the single-sample method was found to be the most robust technique overall, although for all methods measurement error was generally insignificant compared to expected biological variation in GFR. However, at low GFR values measurement errors were shown to affect all methods significantly. Errors in measurement of the doses were found to have the greatest impact on accuracy. Using nuclear medicine techniques 51Cr-ethylenediaminetetra-acetic acid (51Cr-EDTA) is the most commonly used and widely studied exogenous filtration marker. However, 99mTc-diethylenetriaminepenta-acetic acid (99mTc-DTPA) is gaining favour because of a few technical advantages it has over 51Cr-EDTA, its lower cost, and recent issues with the availability of 51Cr-EDTA. In response to a systematic review suggesting that GFR measurement from the plasma clearance of 99mTc-DTPA was inaccurate, a mini meta-analysis was performed that demonstrated excellent agreement between 51Cr-EDTA and 99mTc-DTPA clearance, thus supporting the use of 99mTc-DTPA as a reliable alternative. Where GFR cannot be routinely measured, it is frequently estimated using a creatinine-based equation. The use of any equation first requires validation in the population in which it will be used. In a study evaluating the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in non-cancer, mixed ancestry adults, both equations were found to perform well. However, in a study that evaluated equations in adults with cancer, the GFR estimates were found to be biased and imprecise. This study highlighted the limitations of using estimated GFR for guiding management decisions in cancer patients. A further study evaluated 11 estimating equations in non-cancer and cancer populations of South African children. The accuracy of all estimates was poor, particularly in the cancer group. Given the extensive use of GFR estimates in South Africa, these findings have profound implications for their use in the management of children and adults with cancer in this country. Developing new equations for a specific population requires large datasets and incurs costs that are impractical in most middle- or low-income countries. A simpler alternative is to adapt existing equations. This work demonstrates the application of a relatively simple approach to adapt existing equations, using modest amounts of data and a readily available Microsoft® Excel-based tool. While this approach is simple and likely to require further refinement, its utility was demonstrated in paediatric and adult cancer populations.
How efficient is Technitium -99m labelling of erythrocytes in patients with malaria?
(2011) Ekoume, F. P.; Rubow, S. M.
ENGLISH ABSTRACT: With the expansion of Nuclear Medicine techniques in developing countries, it is essential to ensure a quality imaging procedure. In the case of red cell labelling, any factor which interferes with the labelling can lead to sub-optimal studies. With regard to the high incidence of malaria in sub-Saharan African countries in general and in Cameroon particularly, a high percentage of patients referred to Nuclear Medicine departments also have malaria. The question arose whether the presence of Plasmodium in erythrocytes or anti-malarial medication could affect the labelling of erythrocytes with technetium-99m. The aim of this study was to investigate the impact of Plasmodium and anti-malarial medication on Tc-99m red cell labelling efficiency with in vitro kits in a population with a high prevalence of malaria infection. Approval for this study was obtained from ethics committees of both institutions. Three groups of 30 patients were enrolled in the study after giving informed consent: 1. Smear-negative patients in an area where malaria is endemic (control group M-). 2. Patients with malaria as determined by a positive malaria smear test (group M+). 3. Patients with malaria and on anti- malaria medication (group Mm). From each patient, a 5 ml blood sample was drawn in a heparinised blood collection tube. The red blood cells of each sample were labelled in vitro with Tc-99m, using an in vitro red blood cell kit. Labelling efficiency of the 3 groups was compared. The average labelling efficiency was 98.2% ± 2.3% in malaria-free individuals, 98.6% ± 2.6% in patients with malaria but not on treatment, and 98.6% ± 1.1% in patients with proven malaria on quinine treatment. Non parametric data analysis using the Kruskal-Wallis ANOVA test for the percentage of labelling efficiencies showed a P-value of 0.2117 which was a confirmation that there was no significant difference between the labelling efficiencies for the three groups. Radioactively labelled red blood cells are used in various nuclear medicine studies. Various drug therapies, including antibiotics, are known to either inflict direct or indirect damage to RBCs or their precursors or to impact influx or efflux of Tc-99m-pertechnetate into or out of RBCs, thereby decreasing labelling efficiency to such an extent that poor and inaccurate diagnostic information is obtained. The results of this study indicate that malaria parasites and anti-malarial treatment with quinine do not affect in vitro erythrocyte labelling with Tc-99m, and should thus not interfere with nuclear medicine investigations.
Hybrid imaging using low-dose, localizing computed tomography enhances lesion localization in renal hyperparathyroidism
(Lippincott, Williams & Wilkins, 2014-03) Doruyter, Alexander G.; Hartley, Tharbit; Ameyo, Jonathan W.; Davids, M. R.; Warwick, James M.
Background Preoperative localization of parathyroid lesions is potentially beneficial in renal patients with hyperparathyroidism. The aim of this study was to determine the localizing value of hybrid single-photon emission computed tomography combined with low-dose x-ray computed tomography (SPECT/LDCT) compared with SPECT alone and whether the LDCT improved reader confidence. Patients and methods A retrospective study examined parathyroid scintigraphy results of patients previously referred with a diagnosis of renal hyperparathyroidism. All patients underwent planar scintigraphy using technetium- 99m (99mTc)-pertechnetate, which was immediately followed with 99mTc-sestamibi and SPECT/LDCT ∼ 60 min after sestamibi injection and a delayed static image to assess differential washout. Planar subtraction images were generated. Two nuclear physicians, assisted by a radiologist, reported on planar+SPECT images followed by planar+SPECT/LDCT images. Results Thirty-seven patients (males: 21; females: 16) were included (mean age 39 years, range: 23.9–55.5). Mean creatinine level was 878 μmol/l (109–1839), mean corrected calcium level was 2.42 mmol/l (1.77–3.64), and median parathyroid hormone level was 156.2 pmol/l (2.4 to >201). Twenty-three patients had positive planar and SPECT
Imaging of renal hyperparathyroidism using SPECT/CT with low-dose localizing CT
(Stellenbosch : Stellenbosch University, 2013-12) Doruyter, Alexander Govert George; Warwick, James Matthew; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Division of Nuclear Medicine.
ENGLISH ABSTRACT: Background: Hybrid imaging using single photon emission computed tomography/low dose (x-ray) computed tomography (SPECT/LDCT) is of benefit in preoperative scintigraphy of primary hyperparathyroidism. The role of SPECT/LDCT in preoperative assessment of renal hyperparathyroidism has not yet been examined. The aim of the study was to determine whether SPECT/LDCT conferred any benefit over SPECT alone in terms of detection and/or localization of hyperfunctioning parathyroid tissue in this patient group. Methods: A retrospective study of patients with renal hyperparathyroidism and positive planar and SPECT scintigraphy was undertaken. All patients underwent planar scintigraphy using 99mTc-pertechnetate immediately followed by 99mTc-sestamibi as well as SPECT/LDCT 60 min after sestamibi injection and a delayed static image to assess for differential washout at 2-3 hours. Planar subtraction images were generated. For each patient, two nuclear physicians reported on planar+ SPECT images followed by planar + SPECT/LDCT images (assisted by a radiologist). Confidence for the presence of hyperfunctioning parathyroid tissue as well as confidence of location was scored on a Likert-type scale. Interpretation of planar + SPECT was compared with interpretation of planar + SPECT/LDCT. The impact of LDCT on equivocal lesions and number of ectopic lesions detected was also assessed. Results: Twenty patients (M:13; F:7) imaged between February 2008 and June 2011 were included [mean age: 40 years (24 – 55)]. Mean creatinine was 687 μmol/l (169-1213), mean corrected calcium: 2.55 mmol/l (1.95-3.33) and median PTH 167 pmol/l (2.4 - >201). Thirty-five lesions were detected on planar and SPECT and this was unchanged after assessment of the LDCT data. Confidence for the presence of parathyroid pathology changed in 5 patients (5 lesions) with the addition of LDCT. LDCT changed the mean confidence of parathyroid pathology from 3.17 to 3.29 (p=0.16). Addition of LDCT reduced the number of equivocal lesions from 18 (14 patients) to 14 (10 patients) (p=0.13). The addition of LDCT changed localization in 4 lesions (3 patients). Confidence in localization of pathology changed in 9 lesions (7 patients) and the mean localization confidence score was improved from 4.2 to 4.46 (p=0.002) with LDCT. The number of lesions classified as ectopic increased from 5 (on planar+SPECT) to 8 (with addition of LDCT) (p=0.25). Conclusion: In renal hyperparathyroidism SPECT/LDCT altered localization of lesions detected on planar and SPECT alone and improved reader confidence of localization accuracy. SPECT/LDCT conferred no additional benefit over SPECT in terms of detection, confidence of parathyroid pathology or ability to distinguish equivocal from non-equivocal parathyroid lesions. The addition of LDCT did not detect significantly more ectopic lesions. Whereas the minor improvement in reader confidence of localization (with addition of LDCT) was of questionable clinical significance, we speculate that the changed and presumably improved localization of lesions on SPECT/LDCT had potential clinical impact in a significant proportion of patients. On this basis we recommend the use of hybrid SPECT/LDCT in imaging of renal hyperparathyroidism when surgery is considered.
Implementation of guidelines on hospital radiopharmacy in low-income settings
(Stellenbosch : Stellenbosch University, 2020-12) Ekoume, Fany Pricile; Rubow, Sietske Margarete; Boersma, Hendrikus H.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.
ENGLISH SUMMARY : Although radiopharmacy is more than 50 years old, it is still in a stage of rapid development. This dissertation focuses on quality issues in radiopharmacies in developing countries. Guidelines for radiopharmacy practice in many countries prescribe complex facilities, especially air handling units, and extensive quality assurance and documentation requirements. In developing countries, these guidelines are currently not always met. In numerous countries in Africa, enforcement of the international guidelines would lead to closure of radiopharmacies, and consequently, loss of Nuclear Medicine services. The question arises what the consequences of not meeting the requirements of the guidelines are, and if practice can be improved without major expenditure. This study considered certain aspects of Good Radiopharmacy Practice (GRP) recommendations and collected information from both a relatively well-equipped facility at Tygerberg Hospital (TBH) in South Africa, and a more basic radiopharmacy facility at Yaoundé General Hospital in Cameroon (YGH) to investigate the conditions that will ensure safe and effective products. Factors assessed include efficacy and microbial safety of the radiopharmaceuticals, with some comparison to a state-of-the-art Good Manufacturing Practice (GMP) compliant radiopharmacy at the University Medical Centre Groningen (UMCG) in the Netherlands. An adapted version of the Quality Management Audits in Nuclear Medicine (QUANUM) tool, tailored for the radiopharmacy context, was used to determine the status of practice in the two African radiopharmacies. Once the current situation and product quality in these radiopharmacies was determined, basic, low-cost interventions to minimise deficiencies were implemented at YGH and the effects of the interventions were assessed. Where the necessary level of safety and efficacy could not be met with currently available systems despite interventions, this was reported. The efficacy of radiopharmaceuticals depends on their radiochemical purity. As lack of validation of analytical methods was one of the shortcomings noted in the YGH audit, experimentally validating a cost-effective radiochromatography method to be used at YGH was the first step of corrective actions implemented. As the provision of clean air and maintenance of air handling systems and equipment require a large budget, special emphasis was placed in three further chapters of the dissertation on assessment of microbial contamination of products, and measures to ensure sterility of products. At YGH, we reached better control of microbiological air quality. This was achieved by the implementation of simple microbiological air sampling methods, and subsequent introduction of hygienic and procedural improvements. Sterility testing of SPECT radiopharmaceuticals showed a low contamination rate at both TBH and YGH. Nevertheless, preparing radiopharmaceuticals in a well-maintained laminar air flow cabinet is recommended in order to reduce the risk of contamination of products by airborne microorganisms. The serious consequences that could arise from not meeting GRP requirements, include transmission of microbial infection to patients or administering radiochemically impure products. This dissertation presents the first work evaluating an affordable approach of the implementation of GRP in sub-Saharan Africa. It is highly recommended to all radiopharmacies in the developing world to adapt GRP in their context and to implement an optimised quality assurance programme, striving for continuous improvement.

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