Research Articles (Nuclear Medicine)

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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.
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 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.
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
Metastatiese verkalkinge soos aangetoon met tegnesium-99m-pirofosfaatbeenflikkergrafie : gevalbesprekinge
(Health & Medical Publishing Group, 1982) Louw, N. W.; Klopper, J. F.; Van Heerden, P. D. R.
Two cases of chronic renal failure showing very interesting technetium-99m-pyrophosphate bone scans are presented. In both cases striking uptake of activity was shown in the left ventricle of the heart, the mucosa of the stomach and in both lungs. This picture was attributed to metastatic calcification in these organs. Cases of metastatic calcification demonstrated with bone-seeking agents have been presented previously, but have mainly shown intense uptake of activity in the lungs and in a few cases, and to a lesser degree, in the stomach. However, we believe that our cases are unique in showing especially the left ventricle of the heart as well as the mucosa of the stomach with exceptional clarity.
Methamphetamine dependence with and without psychotic symptoms : a multi-modal brain imaging study
(Elsevier, 2018) Vuletica, Daniella; Dupontc, Patrick; Robertsond, Frances; Warwick, James M.; Zeevaartc, Jan Rijn; Steina, Dan J.
Objective: Methamphetamine dependence can lead to psychotic symptoms which may be mediated by frontal, striatal, limbic, and thalamic regions. There are few neuroimaging data that allow comparison of individuals with methamphetamine dependence who do, and do not, have psychosis. Two complementary imaging techniques were employed to investigate neurocircuitry associated with methamphetamine dependence with and without psychotic symptoms. Methods: Three groups of participants were recruited: methamphetamine dependent (MAA) (N=11), methamphetamine dependent with psychotic symptoms (MAP) (N=14), and controls (N=14). Resting brain glucose metabolism was measured using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and cerebral perfusion was assessed using arterial spin labelling (ASL) magnetic resonance imaging. Results: Methamphetamine abusers (MAA and MAP groups) had decreased glucose metabolism compared to healthy controls in the left insula, left precentral gyrus, and the anterior cingulate cortex. Compared to MAA participants, MAP participants had 1) decreased glucose metabolism in the left precentral gyrus and the left inferior frontal gyrus and 2) increased glucose metabolism in the putamen and pallidum. MAP participants also had increased cerebral perfusion in the right putamen and right pallidum compared to MAA. Conclusion: Findings support the involvement of frontal, striatal, and limbic regions in methamphetamine dependence. Furthermore, they indicate that glucose metabolism and cerebral perfusion in these regions are disrupted in methamphetamine dependent individuals with psychotic symptoms.
Nuclear medicine in South Africa
(HMPG, 2003-08) Warwick, James M.
ENGLISH ABSTRACT: Why should an issue of CME, a publication primarily directed at generalists, be devoted to nuclear medicine? I am reminded from time to time of how unfamiliar many of my colleagues are with this specialty, which is not surprising given the minimal coverage the field receives in already full undergraduate medical school programmes – even specialty-specific postgraduate exposure is often limited. Consequently, there is a paucity of knowledge of the role, indications, availability, and cost of many nuclear medicine procedures in the wider clinical community. Optimal nuclear medicine is heavily reliant on close collaboration with referring clinicians. Two prerequisites for a clear, useful report is a clear definition of the clinical question and the study being appropriate to answer that question. It is primarily the responsibility of nuclear medicine physicians to advise colleagues on what studies can do and, sometimes more importantly, cannot do.
Peptide receptor radionuclide therapy of neuroendocrine tumors : how important is internal dosimetry?
(Health and Medical Publishing Group, 2019) Lawal, I.; Louw, L.; Warwick, James; Nyakale, N.; Steyn, R.; Lengana, T.; Ellmann, A.; Kotze, T.; Vangu, M.; Vorster, M.; Sathekge, M.
No abstract available
PET-CT in brain disorders : the South African context
(AOSIS, 2021-11) Doruyter, Alexander G. G.; Parkes, Jeannette; Carr, Jonathan; Warwick, James M.
Positron emission tomography combined with X-ray computed tomography (PET-CT) has an established role in the management of brain disorders, but may be underutilised in South Africa. Possible barriers to access include the limited number of PET-CT facilities and the lack of contemporary guidelines for the use of brain PET-CT in South Africa. The current review aims to highlight the evidence-based usage of brain Positron emission tomography (PET) in dementia, movement disorders, brain tumours, epilepsy, neuropsychiatric lupus, immunemediated encephalitides, and brain infections. While being areas of research, there is currently no clinical role for the use of PET-CT in traumatic brain injury or in psychiatric or neurodevelopmental disorders. Strategies to expand the appropriate use of PET-CT in brain disorders are discussed in this article.
Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram
(BioMed Central, 2004-10) Carey, Paul D.; Warwick, James; Niehaus, Dana J. H.; Van der Linden, Geoffrey; Van Heerden, Barend B.; Harvey, Brian H.; Seedat, Soraya; Stein, Dan J.
Background: Several studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment. Methods: Single photon emission computed tomography (SPECT) using Tc-99 m HMPAO to assess brain perfusion was performed on subjects with OCD, PTSD, and SAD before and after 8 weeks (SAD) and 12 weeks (OCD and PTSD) treatment with the SSRI citalopram. Statistical parametric mapping (SPM) was used to compare scans (pre- vs post-medication, and responders vs non-responders) in the combined group of subjects. Results: Citalopram treatment resulted in significant deactivation (p = 0.001) for the entire group in the superior (t = 4.78) and anterior (t = 4.04) cingulate, right thalamus (t = 4.66) and left hippocampus (t = 3.96). Deactivation (p = 0.001) within the left precentral (t = 4.26), right mid-frontal (t = 4.03), right inferior frontal (t = 3.99), left prefrontal (3.81) and right precuneus (t= 3.85) was more marked in treatment responders. No pattern of baseline activation distinguished responders from non-responders to subsequent pharmacotherapy. Conclusions: Although each of the anxiety disorders may be mediated by different neurocircuits, there is some overlap in the functional neuro-anatomy of their response to SSRI treatment. The current data are consistent with previous work demonstrating the importance of limbic circuits in this spectrum of disorders. These play a crucial role in cognitive-affective processing, are innervated by serotonergic neurons, and changes in their activity during serotonergic pharmacotherapy seem crucial.
An update on the management of breast cancer in Africa
(BioMed Central, 2017-02-14) Vanderpuye, V.; Grover, S.; Hammad, N.; Prabhakar, Pooja; Simonds, H.; Olopade, F.; Stefan, D. C.
ENGLISH SUMMARY : Background: There is limited information about the challenges of cancer management and attempts at improving outcomes in Africa. Even though South and North Africa are better resourceds to tackle the burden of breast cancer, similar poor prognostic factors are common to all countries. The five-year overall Survival rate for breast cancer patients does not exceed 60% for any low and middle-income country (LMIC) in Africa. In spite of the gains achieved over the past decade, certain characteristics remain the same such as limited availability of breast conservation therapies, inadequate access to drugs, few oncology specialists and adherence to harmful sociocultural practices. This review on managing breast cancer in Africa is authored by African oncologists who practice or collaborate in Africa and with hands-on experience with the realities. Methods: A search was performed via electronic databases from 1999 to 2016. (PubMed/Medline, African Journals Online) for all literature in English or translated into English, covering the terms “breast cancer in Africa and developing countries”. One hundred ninety were deemed appropriate. Results: Breast tumors are diagnosed at earlier ages and later stages than in highincome countries. There is a higher prevalence of triple-negative cancers. The limitations of poor nursing care and surgery, inadequate access to radiotherapy, poor availability of basic and modern systemic therapies translate into lower survival rate. Positive strides in breast cancer management in Africa include increased adaptation of treatment guidelines, improved pathology services including immuno-histochemistry, expansion and upgrading of radiotherapy equipment across the continent in addition to more research opportunities. Conclusion: This review is an update of the management of breast cancer in Africa, taking a look at the epidemiology, pathology, management resources, outcomes, research and limitations in Africa from the perspective of oncologists with local experience.
The use of HEPES-buffer in the production of gallium-68 radiopharmaceuticals – time to reconsider strict pharmacopoeial limits?
(SpringerOpen (part of Springer Nature), 2021-04-01) Le Roux, Jannie; Kleynhans, Janke; Rubow, Sietske
ENGLISH ABSTRACT: HEPES (4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) is a buffer that is used in the radiolabelling of gallium-68 compounds. The beneficial effects of HEPES on molar activity in bioconjugates have been well described. Current strict regulations on the HEPES content in radiopharmaceuticals limit its use when intended for parenteral administration. This short communication summarizes data from the literature on the toxicity of HEPES in dogs after intravenous infusion and the subsequent use in humans. We also highlight the use of HEPES in an FDA labelled intravenous drug formulation. Regulatory institutions may consider this data to review current strict limits.
Validation of a cost-effective alternative for a radiochromatography method to be used in a developing country
(SpringerOpen (part of Springer Nature), 2020-04-10) Ekoume, F. P.; Boersma, H. H.; Dong a Zok, F.; Rubow, S. M.
Introduction: The radiochemical purity (RCP) of technetium-99m labelled radiopharmaceuticals (RP) is important to ensure optimal scintigraphic image quality. In low-income settings, it may not be possible to use compendial analytical methods or expensive equipment for radiochemical purity analysis. All radiochemical analysis methods should however be validated against compendial or otherwise proven methods. To ensure the efficacy of RP prepared at Yaoundé General Hospital (YGH) Cameroon, this study cross-validated a cost-effective routine chromatographic method using a simple survey meter technique. A GMP-compliant method used at the University Medical Center Groningen (UMCG), the Netherlands was used as the comparator. Methods: Sestamibi, HMDP and DMSA kits currently used at YGH were reconstituted at UMCG with about 2000 MBq of freshly eluted sodium pertechnetate as described by the manufacturer, and spiked with eluate of the same generator to obtain a range of impurity concentrations. Samples of technetium-99m RP were spotted on 1 × 10 cm iTLC-SG strips and developed in appropriate mobile phases. Each strip was first scanned on the chromatogram-scanner used at the UMCG (standard method), and immediately thereafter the strip was cut in two pieces and radioactivity from each portion was counted with a small survey meter from YGH. The percentage RCP for each TLC strip was calculated using both counting methods. Internationally recommended validation parameters and acceptance criteria were used. Student’s paired t-test or ANOVA were used with ‘no significant difference’ designated at a 95% confidence-interval (P ≥ 0.05). Linearity of the survey meter was determined for Tc-99m. Readings obtained with the survey meter were also plotted against the scanner results. Results and discussion: The proposed method proved to be accurate (CV of mean RCP < 2), precise (RSD < 2%), linear (slope close to 1, r2 ≥ 0.99) within the RCP range of approximately 80% to 100%, and robust (P > 0.05). LOD and LOQ were determined for the survey meter. Specificity depends on chemical separation. As we were validating the suitability of a method to quantify radioactivity, specificity was not included in the validation parameters. Conclusion: The proposed method compared well with the standard method and is suitable as a reliable low cost method for limited resource settings.
Validation of equations to estimate glomerular filtration rate in South Africans of mixed ancestry
(Health & Medical Publishing Group, 2020-02-26) Holness, Jen L.; Bezuidenhout, K.; Davids, M. R.; Warwick, J. M.
Background. The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are two commonly used formulae to estimate glomerular filtration rate (GFR) in adults. The CKD-EPI equation is recommended in current international and local guidelines for the diagnosis and management of chronic kidney disease (CKD), unless an alternative equation has been shown to have superior accuracy. Validation and comparison of the equations in local populations are therefore required. Previous studies have reported on the accuracy of these prediction equations in black South Africans and those of Indian ancestry. Objectives. To evaluate the MDRD and CKD-EPI equations in South African (SA) adults of mixed ancestry. Methods. In all participants, GFR was measured (mGFR) from plasma clearance of 99mTc-diethylenetetraaminepenta-acetic acid (99mTc-DTPA), using a standardised technique. Serum creatinine assays were isotope dilution mass spectrometry traceable. GFR was estimated (eGFR) using the MDRD and CKD-EPI equations, with and without the black ethnicity factor. The agreement, bias, precision and accuracy of each equation was determined. Results. Eighty adults were included (30 male, median age 39 years, median GFR 59 mL/min/1.73 m2). Sixty-eight had a diagnosis of CKD, 10 were potential kidney donors, and 2 were healthy volunteers. Both equations, without the black ethnicity factor, had good agreement with measured GFR. The equations tended to overestimate GFR, with bias of 1.6 and 7.9 mL/min/1.73 m2 for the MDRD and CKD-EPI equations, respectively. The interquartile ranges of the differences were 15.9 and 20.2 mL/min/1.73 m2, and as a measure of accuracy, the percentages of estimates that fell within 30% of the mGFR (P30) were 80% and 72.5% (p=0.18). For identification of individuals with a GFR <60 mL/min/1.73 m2, the sensitivity of MDRD eGFR was 97.3% and that of CKD-EPI eGFR was 97.1%. Conclusions. The MDRD and CKD-EPI equations have shown satisfactory and comparable performance in this SA mixed-ancestry adult population, with the MDRD equation marginally less biased than the CKD-EPI.
Ventilasiestudies van die long met kripton-81m
(HMPG, 1981-08) Klopper, J. F.; Van Heerden, P. D. R.; Baard, W. P.
During a 2-year study period it was found that krypton-81m was useful in routine clinical practice. During this period 1563 technetium-99m perfusion studies and 807 krypton-81m ventilation studies were performed. A distinct advantage of krypton-81m was the ease with which multiple views could be obtained. These views could be directly compared with those of preceding perfusion studies. However, interruptions in the regular supply of rubidium-81/krypton-81m generators affected 17.1% of perfusion studies and xenon-127 should be a suitable substitute for these periods.

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