Research Articles (Nuclear Medicine)

Permanent URI for this collectionhttp://hdl.handle.net/2263/2419

For inquiries regarding this collection or items in the collection, please contact : Susan Scheepers
Tel.: +27 12 354 1940

Browse

Now showing 1 - 20 of 252

Radiotheranostics in low-and middle-income countries : challenges, practice, and prospects
Lawal, Ismaheel Opeyemi; Ndlovu, Honest; Kabunda, Joseph; Mokoala, Kgomotso M.G.; Sathekge, Mike Machaba (Thieme Gruppe, 2025-10-14)
There is a global rise in the number of new cancer diagnoses and cancer deaths. Rising new cancer diagnoses and deaths from low- and middle-income countries (LMICs) are the biggest contributors to this global trend. Efforts geared toward prevention, timely diagnosis, effective treatment, and efficient cancer survivorship programs are needed to address the rising scourge of cancer in LMICs. Radiotheranostics entails using radiopharmaceuticals for diagnostic imaging and therapy of diseases. Functional imaging, as in radiotheranostics, is more sensitive for disease detection and treatment response assessment than conventional cross-sectional imaging. Therefore, radiotheranostics has the potential to address some of the strategies to curtail the rising scourge of cancer and its mortality in LMICs, including timely diagnosis, effective management, and disease surveillance. Many key issues hinder the widespread availability, access, and utilization of nuclear medicine (NM) and radiotheranostics services in LMICs. These issues include scarcity of trained (NM) professionals, lack of training for (NM) personnel, poor infrastructure, inadequate awareness of NM and radiotheranostics, poor funding, and poorly conceived regulations that stifle NM practice. Despite these hindrances, many success stories have emerged from LMICs regarding clinical application of radiotheranostics. For example, many practice-defining studies have been published by groups from LMICs regarding prostate-specific membrane antigen-targeted imaging and therapy of prostate cancer. Specifically, notable contributions have been made to the literature by groups from South Africa, India, and Türkiye on the safety and efficacy of 225Ac-PSMA-617 for therapy of advanced prostate cancer. Through the intervention of many international organizations, governments, and private sectors, there has been a steady improvement in the awareness, availability, access, and utilization of NM and radiotheranostics services in LMICs.
Predictive relationships between AGTR1 and ACE2 polymorphisms for hypertension and COVID-19 in patients at a Tshwane Academic Hospital : a preliminary study
Chalwe, Joseph Musonda; Moholisa, Retsilisitsoe Raymond; Modipane, Ndimo Rahab; Mbambara, Saidon Herbert; Matobole, Relebohile; Moetlhoa, Boitumelo; Sathekge, Mike Machaba; Kgatle, Mankgopo (MDPI, 2026-02-28)
BACKGROUND : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), exploits angiotensin-converting enzyme 2 (ACE2) for cell entry, implicating the renin–angiotensin system (RAS) in disease pathogenesis. Hypertension (HT), a major comorbidity, is strongly influenced by genetic factors within RAS, including angiotensin ii receptor type 1 (AGTR1) and ACE2) polymorphisms. However, data on these variants in African populations remain scarce. This study investigated associations between AGTR1 and ACE2 single-nucleotide polymorphisms (SNPs), HT, and COVID-19 severity in patients at a Tshwane Academic Hospital. METHODS : We genotyped AGTR1 and ACE2 SNPs in 94 PCR-confirmed COVID-19 patients using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry. Clinical data were extracted from hospital records. Ordinal logistic regression models assessed relationships between SNPs, HT, and COVID-19 severity. RESULTS : The cohort (mean age: 53.9 years; HT prevalence: 54.9%) exhibited mild (54.9%), moderate (18.6%), and severe (26.5%) COVID-19. Although the rs2106809 A genotype appeared to be associated with lower odds of severe disease (OR = 0.39, 95% CI: 0.14–1.08, p = 0.04), this observation should be interpreted with caution given the limited sample size of this study. Other SNPs and clinical variables showed no significant associations. CONCLUSIONS : This exploratory study represents the first description of AGTR1 and ACE2 SNP patterns in COVID-19 patients from Tshwane. While the rs2106809 variant may indicate a possible protective trend, the evidence remains preliminary. Age correlated with severity. Larger, multi-ethnic studies are needed to confirm these findings.
Organocatalytic Michael addition of β-ketoesters and ethenesulfonyl fluoride: access to chiral δ-sultones via SuFEx chemistry
Govender, Kimberleigh B.; Kruger, Hendrik G.; Govender, Thavendran; Ebenhan, Thomas; Arvidsson, Per I.; Naicker, Tricia (Georg Thieme Verlag, 2026-02)
Sultones have been gaining popularity within medicinal chemistry due to their vast biological activity; however, access to chiral δ-sultones remains limited. In this study, we have developed an organocatalyzed Michael addition reaction between β-ketoesters and ethenesulfonyl fluoride using a bifunctional thiourea catalyst. This methodology resulted in 11 Michael adducts in yields up to 99% and enantioselectivities up to 84%. Subsequent cyclization under sulfonyl fluoride exchange conditions afforded seven novel chiral δ-sultones in low to moderate yields, generally preserving the enantioselectivity. This work presents an innovative strategy for efficiently synthesizing chiral δ-sultones.
Beyond [177Lu]Lu-PSMA : a meta-analysis of safety and efficacy of emerging PSMA radioligand therapy agents
Abdlkadir, Ahmed Saad; Al-Adhami, Dhuha; Moghrabi, Serin; Sathekge, Mike Machaba; Kreiss, Michael; Estrada-Lobato, Enrique; Shi, Hongcheng; Al-Ibraheem, Akram (BMC, 2026-03-23)
BACKGROUND: This systematic review and meta-analysis evaluates the safety and efficacy of emerging prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) agents used beyond [¹⁷⁷Lu]Lu-PSMA in metastatic castration-resistant prostate cancer (mCRPC). METHODS: Systematic searches of PubMed, Web of Science, and Scopus were performed from inception until November 3, 2025. Studies reporting objective response rate (ORR), disease control rate (DCR), and/or toxicity outcomes were included. Meta-analytic pooling, assessment of publication bias, heterogeneity analyses, and subgroup evaluations were conducted using Stata software. RESULTS: A total of 33 studies published between 2017 and 2025 met inclusion criteria, encompassing 3625 therapy cycles administered to 1525 patients. The pooled DCR was 86% (95% CI: 82–90%), and the pooled ORR was 57% (95%CI: 50–63%). [²²⁵Ac]Ac-PSMA monotherapy, evaluated in 17 studies, achieved pooled DCR and ORR values of 88% and 62%. Eight studies assessing [¹⁷⁷Lu]Lu/[²²⁵Ac]Ac-PSMA tandem therapy reported pooled DCR and ORR values of 84% and 51%. Five studies on [¹⁶¹Tb]Tb-PSMA demonstrated pooled DCR and ORR values of 81% and 46%. [¹³¹I]PSMA therapy, reported in three studies, resulted in a pooled DCR of 75% and pooled ORR of 48%. Adverse events were documented in 32 studies, with a pooled incidence of 26%. Most events were low-grade and reversible. Xerostomia and anemia were the most frequently reported toxicities, with xerostomia particularly associated with [²²⁵Ac] Ac-PSMA–containing regimens. CONCLUSION: These findings underscore the promising therapeutic potential of emerging PSMA RLT agents beyond [¹⁷⁷Lu]Lu-PSMA, with favorable biochemical responses and manageable safety profiles. Future large-scale prospective studies are essential to define optimal therapeutic roles and expand treatment opportunities for patients with mCRPC.
NETosis associates with human TB lung tissue destruction and disease pathogenesis
Fisher, Kimone L.; Mpotje, Thabo; Nargan, Kievershen; Moodley, Denelle; Rajkumar-Bhugeloo, Kerishka; Baiyegunhi, Omolara O.; Naidoo, Threnesan; Madansein, Rajhmun; Sathekge, Mike Machaba; Leslie, Alasdair; Tomlinson, Gillian; Pollara, Gabriele; Noursadeghi, Mahdad; Steyn, Adrie J.C.; Ndung'u, Thumbi; Marakalala, Mohlopheni J. (Springer, 2026-07-13)
Understanding drivers of tuberculosis (TB) associated lung pathological damage is vital in identifying targets for host directed therapies (HDT). NETosis is a neutrophil specific cell death characterized by release of neutrophil extracellular traps (NETs). The role of NETosis in TB-associated lung damage and disease pathogenesis is still poorly understood. We analysed human lung TB granuloma samples using a proteomics approach, which revealed enrichment of neutrophil-associated proteins in necrotic regions of caseous and cavitary granulomas. Using immunohistochemistry (IHC), we validated the abundance of neutrophil-associated proteins, including myeloperoxidase (MPO), cytochrome b-245 beta chain (CYBB) and neutrophil cytosolic factor 1 (NCF1), as well as NETosis markers, neutrophil elastase (NE) and citrullinated H3, in necrotizing caseum of human TB granulomas. MPO protein expression was also more abundant in the plasma of TB patients compared to healthy and latently infected (LTBI) participants. MPO directly correlated with an inflammatory disease marker, IP-10. In addition, MPO and IP-10 colocalized in caseous lesions. In-vitro drug inhibition assays were used to investigate potential drivers of NETosis, with pharmaceutical inhibition of MPO, NE and CYBB resulting in reduction of NETosis induced by Mycobacterium tuberculosis (Mtb). Using RT-qPCR we analysed the expression of 18 neutrophil associated genes in the blood of healthy (n = 20), latent TB infection (LTBI) (n = 20) and TB (n = 30) participants. We found that MPO, NCF1 and NCF2 were upregulated in the TB group. Furthermore, the NETosis-associated genes were induced in a human standardized antigen challenge model. Our data shows evidence of NETosis as an associate of lung pathological damage in TB and identifies key drivers of the neutrophil cell death that can be intercepted as potential HDT targets to reduce neutrophil driven lung pathological damage.
Ethical dilemmas and medicolegal implications of nuclear medicine imaging in dementias
Kabunda, Joseph; Ndlovu, Honest; Chimbabantu, Kaoma; Knoesen, Zane; Mashigoane, Khomotso; Mokoala, Kgomotso M.G.; Sathekge, Mike Machaba (Springer, 2025-12)
PURPOSE : Positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) increasingly support early dementia diagnosis yet generate complex ethical and medicolegal questions. This review synthesises current evidence to guide responsible clinical and research use. METHODS : A narrative review was undertaken in accordance with SANRA guidance. PubMed (n = 286), Scopus (n = 201) and the first 200 Google Scholar records were searched for English-language publications dated January 2005–May 2025 using (“dementia” OR “Alzheimer disease”) AND (“PET” OR “SPECT” OR “positron emission tomography”) AND (“ethics” OR “medicolegal” OR “informed consent” OR “biomarker disclosure”). De-duplication reduced 687 hits to 622 unique citations. Titles, abstracts and full texts were screened against predefined criteria focused on ethical or legal aspects of PET/SPECT, retaining 53 papers. Targeted manual searches of guideline repositories, policy documents and reference lists added 49 further sources (professional guidelines, consensus statements, policy papers and systematic reviews). Altogether, 102 publications were narratively reviewed. RESULTS : Ethical themes centred on (i) obtaining valid consent from cognitively impaired persons, (ii) communicating probabilistic biomarker findings, and (iii) ensuring equitable access to costly imaging and downstream therapies. Major medicolegal issues included the evolving diagnostic standard of care, liability for misinterpretation, the influence of pre-clinical findings on legal-capacity determinations, and gaps in data-privacy regulation for neuroimaging biomarkers. CONCLUSIONS : PET and SPECT provide clinical benefit yet impose substantive ethical and legal obligations. Capacity-sensitive consent, transparent result disclosure, strict adherence to appropriate-use criteria and stronger anti-discrimination and privacy statutes are recommended to protect patients while maximising the value of nuclear-medicine imaging in dementia.
Evaluating the diagnostic utility of [68Ga]Ga-Pentixafor in solid tumors : a systematic review
Ruzzeh, Saad; Abdlkadir, Ahmed Saad; Al-Alawi, Hasan; Lopci, Egesta; Sathekge, Mike Machaba; Moghrabi, Serin; Obeidat, Shahed; Al-Ibraheem, Akram (Springer, 2025-10)
The C-X-C motif chemokine receptor 4 (CXCR4) has emerged as a critical molecular imaging target in various malignancies due to its central role in tumor progression, metastasis, and resistance to therapy. Among the imaging modalities developed to exploit this target, [68Ga]Ga-Pentixafor—a positron emission tomography (PET) radiopharmaceutical—has shown potential in diagnostic imaging. However, its diagnostic utility in solid tumors remains relatively underexplored, particularly in comparison to the widely utilized [18F]fluorodeoxyglucose ([18F]FDG) PET/CT. Comprehensive literature search was performed across PubMed, Scopus, Web of Science and Embase, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included those reporting CXCR4-targeted PET imaging in solid tumors, with data on lesion detection, semiquantitative uptake values including maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR). Data extraction focused on study design, patient demographics, tumor types, imaging protocols, and key findings. The quality of included studies was assessed using standardized risk-of-bias tools using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. This systematic review analyzed data from 26 studies, encompassing 831 patients with various solid malignancies to assess the diagnostic utility of [68Ga]Ga-Pentixafor PET/CT. Tracer uptake varied significantly among tumor types, with higher SUVmax values observed in adrenocortical carcinoma, small cell lung cancer, and desmoplastic small round cell tumors, while lower uptake was noted in breast cancer, glioblastoma, and melanoma. Certain malignancies, such as prostate cancer, pleural mesothelioma, and colorectal carcinoma, exhibited minimal or absent CXCR4 expression on PET imaging. A correlation between in vivo PET uptake and histopathologic CXCR4 expression was evident in specific tumor types, though heterogeneity in receptor expression was reported. When compared to [18F]FDG PET/CT, [68Ga]Ga-Pentixafor PET/CT demonstrated lower lesion detectability, highlighting its potential as a theranostic tool for CXCR4-targeted therapies rather than a primary diagnostic modality. [68Ga]Ga-Pentixafor PET/CT represents a promising, yet evolving, tool in oncology. While its diagnostic performance may not rival that of [18F]FDG PET/CT across all tumor types, its theranostic potential underscores its value in the precision medicine landscape.
Plant-derived modulators of tumor metabolism as novel, efficacious, and low-toxicity therapeutic agents for cancer treatment
Maphoso, Tania Mmapule; Ramali, Dakalo Portia; Mulaudzi, Thanyani Victor; Maharaj, Vinesh J.; Driver, Cathryn Helena Stanford; Damane, Botle Precious (MDPI, 2026-05)
Metabolic reprogramming is a core hallmark of malignancy, enabling tumor cells to sustain rapid proliferation, evade immune elimination, and develop resistance to therapy. Although a wide range of plant-derived phytochemicals exhibit anticancer activity with comparatively low toxicity, their capacity to disrupt specific metabolic dependencies exploited by tumors has not been comprehensively synthesized. This review brings together current mechanistic evidence showing how major phytochemical classes, including polyphenols, terpenes and terpenoids, glucosinolates, and alkaloids, interfere with pathways central to tumor metabolic fitness, such as aerobic glycolysis, pentose phosphate pathway flux, mitochondrial substrate oxidation, glutamine dependence, and redox homeostasis. It further introduces a pathway-focused framework that links phytochemical mechanisms to quantifiable metabolic outcomes and highlights their potential to remodel the tumor microenvironment by altering nutrient competition, oxidative stress responses, and hypoxia-driven signaling. Key barriers such as poor systemic bioavailability, rapid metabolic degradation, and limited tissue penetration are assessed alongside emerging formulation and delivery strategies designed to enhance therapeutic exposure while preserving low-toxicity profiles. Mapping these mechanistic insights onto clinical development needs allows prioritization of specific phytochemical-metabolic pathway pairs with the strongest potential for translation. This positions plant-derived metabolic disruptors as promising candidates for next-generation, low-toxicity anticancer therapies that strategically exploit defined metabolic vulnerabilities.
Alternative treatment for recurrent keloids : initial clinical experience with Rhenium-188 using a specialized device
Mokoala, Kgomotso M.G.; Nonjola, lINDA; Moeng, Thabiso; Corbett, Ceceila; Magwaza, Martin; Dahlhoff, Gerhard; Brown, Shannon; Vetter, Nicholas; Vorster, Mariza; Sathekge, Mike Machaba (Springer, 2025-07)
INTRODUCTION : Keloids have proved challenging to manage with various therapies providing variable success rates and recurrences. Alternative therapies or a multimodal approach is often necessary to ensure complete eradication and prevent recurrence. The use of radioactive creams or patches embedded with Holmium-166, Phosphorus-32 for superficial skin lesions has been documented to be safe and effective. The use of Rhenium-188 has proved effective in non-melanoma skin cancers. We report on the initial experience with Rhenium-188 SCT in the treatment of recurrent keloid lesions. METHODS : Patients with recurrent keloid lesions were recruited for therapy with Rhenium-188. These patients had failed most forms of therapy including surgery, intralesional steroids and radiation therapy. Treatment with 188Re via a specialized unit (Rhenium SCT -Oncobeta) was applied onto the keloid lesion. A personalized treatment time was calculated for every patient. Topical 188Rhenium delivered as a jelly like matrix containing an insoluble dirhenium-heptasulfide was applied to every target lesion in a single session. The goal is to deliver 30 Gy to the deepest part of the lesion per session (3 mm). Patients were followed up at 2 weeks, 1, 3, 6 and 12 months for side effects as well as clinical and cosmetic outcomes. RESULTS : A total of 58 lesions were treated. Majority of the lesions were in the head and neck region. The smallest area for treatment was 0.25cm2 and the largest area treated was 46.25cm2. With the exception of four patients (2 sessions to the same lesion), all the other patients received a single session of therapy. The mean activity administered was 256,7MBq (range: 35MBq- 663,50MBq). The treatment time averaged 350.89 min (range: 85-1304 min). There was complete response in 72% of the lesions. Hypopigmentation was the commonest expected long term side effect. After a median follow-up period of 37 months (range: 7-53), there was a 7% recurrence rate. CONCLUSION : Treatment with 188Re is a great alternative in patients with keloids that have had minimal success with other therapies. The use of the specialized applicator system provides great flexibility, reduced morbidity and great results that are comparable to other therapies.
Wastewater-based surveillance for SARS-CoV-2 in rural Northern South Africa : implementation and observations from 2021-2022
Tambe, Lisa Arrah Mbang; Munzhedzi, Mukhethwa; Mathobo, Phindulo; Edokpayi, Joshua Nosa; Mavhandu-Ramarumo, Lufuno Grace; KhozaJohnson, Rabia; Street, Renee; Bessong, Pascal Obong (Elsevier, 2026-06)
Globally, wastewater-based epidemiology (WBE) is employed to assess the distribution and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. This study reports SARS-CoV-2 trends, circulating variants of concern (VOCs), and predicted prevalence of infections in the rural Vhembe and Mopani districts, in Northern South Africa between January 2021 and June 2022, using WBE. Weekly, a grab sample of wastewater influent was collected from seven wastewater treatment plants and one waste sedimentation pond and analyzed for viral genetic material. The trends showed three periods of increased detection of SARS-CoV-2 viral RNA in wastewater which corresponded to the third and fourth waves during the COVID-19 pandemic in South Africa. From the wastewater surveillance reported herein, VOCs detected in the study sites were Delta (in January 2021) and Omicron (in February 2021). These detections from wastewater were earlier than what had been reported from clinical surveillance in South Africa and in other parts of the world. Therefore, WBE has the potential to serve as an early warning system for rural parts of South Africa, and in similar settings as well. Consequently, making possible nation-wide surveillance systems for pathogens capable of causing widespread epidemics. The absence of municipal sewerage systems is common in African communities. Thus, studies to strengthen pandemic preparedness measures, as well as improvement in wastewater treatment infrastructure in the study communities, are also needed. Finally, wastewater-based surveillance as part of long-term strategy is relevant for early detection of novel SARS-CoV-2 variants.
An insight to nanoliposomes as smart radiopharmaceutical delivery tools for imaging atherosclerotic plaques : positron emission tomography applications
Sebatana, Reabetswe; Kudzai, Kahwenga D.; Magura, Allan; Mdlophane, Amanda H.; Zeevaart, Jan Rijn; Sathekge, Mike Machaba; Kahts, Maryke; Mdanda, Sipho; Witika, Bwalya Angel (MDPI, 2025-02-12)
Atherosclerosis is a chronic progressive disease which is known to cause acute cardiovascular events as well as cerebrovascular events with high mortality. Unlike many other diseases, atherosclerosis is often diagnosed only after an acute or fatal event. At present, the clinical problems of atherosclerosis mainly involve the difficulty in confirming the plaques or identifying the stability of the plaques in the early phase. In recent years, the development of nanotechnology has come with various advantages including non-invasive imaging enhancement, which can be studied for the imaging of atherosclerosis. For targeted imaging and atherosclerosis treatment, nanoliposomes provide enhanced stability, drug administration, extended circulation, and less toxicity. This review discusses the current advances in the development of tailored liposomal nano-radiopharmaceutical-based techniques and their applications to atherosclerotic plaque diagnosis. This review further highlights liposomal nano-radiopharmaceutical localisation and biodistribution—key processes in the pathophysiology of atherosclerosis. Finally, this review discusses the direction and future of liposomal nano-radiopharmaceuticals as a potential clinical tool for the assessment and diagnosis of atherosclerotic plaque.
PET imaging of mycobacterial infection : transforming the pipeline for tuberculosis drug development
Kleynhans, Janke; Gouws, Christiaan A.; Ebenhan, Thomas (Nature Research, 2025)
Improved PET/CT radiopharmaceuticals can better visualize and monitor tuberculosis and enable real-time pharmacological drug profiling in vivo. PET/CT imaging can therefore be used to study in animal models the changes in tissue pathology in tuberculosis infection, such as mycobacterial latency, tuberculoma formation, lung cavitation or calcification, and extrapulmonary disease. This Perspective aims to critically evaluate the current and future contribution and role of PET imaging in anti-tuberculosis drug development.
SPARC : the standardised prostate-specific membrane antigen positron emission tomography/computed tomography analysis and reporting consensus : a Delphi analysis
Herrmann, Ken; Walz, Jochen Christoph; MacLennan, Steven J.; Briganti, Alberto; Cornford, Philip A.; Czernin, Johannes G.; Eiber, Matthias J.; Fanti, Stefano; Fendler, Wolfgang Peter; Fizazi, Karim S.; Gafita, Andrei; Gillessen, Silke; Goffin, Karolien; Hadaschik, Boris; Hofman, Michael S.; Hope, Thomas A.; Maurer, Tobias; Morgans, Alicia K.; Morris, Michael J.; Murphy, Declan G.; Oprea-Lager, Daniela E.; Ost, Piet; ÓSullivan, Joe M.; Rouvière, Olivier; Sandhu, Shahneen; Sartor, Oliver; Sathekge, Mike Machaba; Tempany, Clare; Witjes, Wim; Emmett, Louise; Bjartell, Anders S. (Elsevier, 2026-03)
BACKGROUND AND OBJECTIVE : Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an evolving diagnostic tool for prostate cancer. There is a need to harmonise existing guidelines and reporting recommendations for PSMA PET/CT. The Standardised PSMA PET/CT Analysis and Reporting Consensus (SPARC) project aims to consolidate classifications and recommendations by a multidisciplinary and international group of experts under one cohesive framework, establishing a dynamic and evolving structure for PSMA PET/CT reporting. METHODS : We employed a cross-sectional iterative process to define opinions and evaluate consensus. Thirty expert panel members, representing diverse specialities and geographic areas, were selected. A methods expert led the design, data collection, and analysis. Five groups of international multidisciplinary prostate cancer experts convened for literature review and formulation of statements on standardised reporting, detection, primary staging, biochemical recurrence, and treatment response. The groups compiled 91 statements for a two-round modified Delphi survey. The “RAND appropriateness method” was used for the analysis. KEY FINDINGS AND LIMITATIONS : Consensus increased to 93% between two rounds. The panel endorsed and adopted the following frameworks for reporting of PSMA PET/CT: molecular imaging PSMA for expression level and certainty, miTNM by PROMISE for reporting of PSMA PET/CT, the PRIMARY score for intraprostatic staging, PSMA volume, mean standardised uptake value, and maximum standardised uptake value (SUVmax). There were uncertainty about correlating PSMA PET/CT with conventional imaging risk groups in newly diagnosed metastatic prostate cancer and a lack of agreement that clinical management plans based upon PSMA PET/CT improved outcomes. There was consensus that SUVmax should be reported regionally, rather than reporting a single site. There were insufficient data to standardise a definition of response or progression by PSMA PET/CT. CONCLUSIONS AND CLINICAL IMPLICATIONS : SPARC provides a standardised PSMA PET/CT analysis and reporting consensus to serve as a future reference for PSMA PET/CT reporting. Integration of common PSMA PET reporting criteria under one umbrella improves the explanation of imaging findings between imaging experts and treating clinicians for clinical implementation.
Mini-review and situation report on the role and usefulness of nuclear medicine imaging for malaria
Duvenhage, Janie; Zeevaart, Jan Rijn; Sathekge, Mike Machaba; Ebenhan, Thomas (Springer, 2026-01)
Malaria remains one of the deadliest parasitic diseases globally. Delay or failure in treatment can lead to the development of severe malaria. Severe malaria, an understudied multisystem disease, affects the host’s organs and can lead to several syndromes and serious complications, some effecting life-long neurological and cognitive sequela. There is a lack in knowledge regarding the molecular mechanisms underlying severe malaria pathogenesis, and research has mostly relied on post-mortem studies and animal models, both of which lack translatability to human malaria. This review presents the clinical nuclear imaging techniques used in malaria. Although the presented radiopharmaceuticals have added value to understand some aspects of severe malaria, there has been in stagnation in development of more malaria-specific radiopharmaceuticals. This manuscript highlights the current limitations for implementing improved radiopharm
Recent advances in multimodal imaging of infections : research highlights using nuclear-optical imaging
Welling, Mick M.; Driver, Cathryn Helena Stanford; Koatale, Palesa Caroline; Naicker, Tricia; Ebenhan, Thomas (Springer, 2026-04)
Multimodal imaging using hybrid imaging agents is a promising strategy for diagnosing and evaluating pathologies after image-guided surgical interventions. Combining optical and radioactive imaging techniques provides a comprehensive approach to monitoring and diagnosing infections, which would be more effective than routine nuclear clinical tracers for SPECT or PET imaging, thereby enabling more effective treatment as in image-guided surgery. This review summarizes the latest developments in hybrid imaging agents and vectors for radioactive and optical imaging of bacterial, fungal, and viral infections. We pinpoint the pitfalls in the current preclinical landscape for developing infection imaging tracers. Besides diagnosing and tracking pathogens, the role of optical imaging in diagnosing and aiding antimicrobial interventions, including image-guided surgery, is discussed. Finally, practical considerations are addressed for multimodal workflow challenges in preclinical infection imaging with hybrid tracers.
Imaging of infection in nephro-urology : a practical nuclear medicine–focused review
Mokoala, Kgomotso M.G.; Kaoma, Chimbabantu; Jibril, Farida; Kabunda, Joseph; Sathekge, Mike Machaba (Elsevier, 2026)
Infection of the nephro-urological system remains a common and clinically challenging problem, particularly in patients with atypical presentations, prior instrumentation, or underlying immunosuppression. Conventional anatomical imaging plays a central role in identifying obstruction, collections, and complications but is often limited in distinguishing active infection from sterile inflammation or post-interventional change. Nuclear medicine techniques provide complementary functional and molecular information that can clarify disease activity, define extent, and influence patient management. This review presents a practical, nuclear medicine-focused overview of imaging approaches for nephro-urological infection. Established techniques, including ⁹⁹ᵐTc-DMSA imaging, radiolabelled white blood cell scintigraphy, and 18F-FDG PET/CT, are discussed with emphasis on tracer biology, physiological renal handling, and common interpretive pitfalls. Clinical scenarios such as acute and chronic pyelonephritis, renal abscess, transplant infection, and device-related infection are used to illustrate appropriate tracer selection and integration with anatomical imaging. Special populations, including paediatric patients, immunocompromised individuals, and renal transplant recipients, are considered, alongside practical algorithms and teaching points aimed at improving clinical applicability. Emerging developments in bacteria-specific tracers, quantitative imaging, and hybrid modalities are also reviewed. By adopting a biologically informed and question-driven approach, nuclear medicine can play an increasingly important role in the diagnosis and management of nephro-urological infection. KEY TEACHING POINTS • Nuclear medicine imaging of nephro-urological infection reflects biological activity and inflammatory response, providing information beyond structural imaging. • Physiological renal tracer handling and urinary excretion are major challenges; optimized preparation, delayed imaging, and hybrid techniques are essential for accurate interpretation. • ¹⁸F-FDG PET/CT offers high sensitivity and whole-body assessment and is particularly valuable in complicated infection, renal transplant recipients, and fever of unknown origin. • Radiolabelled white blood cell scintigraphy provides greater specificity for active infection and is especially useful in chronic, recurrent, or device-related infection. • ⁹⁹ᵐTc-DMSA is best suited for evaluating renal cortical involvement and long-term sequelae rather than distinguishing active infection. • Selection of imaging technique should be question-driven, tailored to disease acuity, chronicity, and clinical context. • Nuclear medicine imaging is most effective when integrated into a multimodality diagnostic pathway alongside ultrasound, CT, and MRI. • Awareness of common pitfalls, including post-procedural inflammation and malignancy-related uptake, is essential to avoid false-positive interpretations. • When appropriately applied, nuclear medicine imaging can directly influence management, supporting targeted intervention and rational antimicrobial stewardship.
Safety and efficacy of peptide receptor radionuclide therapy for advanced medullary thyroid cancer : a systematic review and meta-analysis
Abdlkadir, Ahmed Saad; Al-Adhami, Dhuha; Shi, Hongcheng; Sathekge, Mike Machaba; Sheikha, Areej Abu; Mohamad, Issa; Kreissl, Michael; Al-Ibraheem, Akram (BioMed Central, 2026-02)
Please read abstract in the article.
The implication of aberrant NRF2 activation in management of female cancers
Kgatle, Mankgopo; Mbambara, Saidon; Fadebi, Olalekan; Kabunda, Joseph; Kaoma, Chimbabantu; Dlangalala, Thobeka Nomzamo; Nxele, Siphesihle Robin; Modipane, Ndimo; Serite, Thato; Mokoala, Kgomotso M.G.; Mashamba-Thompson, Tivani Phosa; Sathekge, Mike Machaba (Frontiers Media, 2025-11-17)
The overactivation of NRF2 (Nuclear factor erythroid 2-related factor 2) in female malignancies is an emerging field of study with significant implications for treatment efficacy. NRF2 plays a pivotal role in managing inflammation-induced oxidative stress, which is crucial components of the tumor microenvironment. Acting as a transcription factor and basic leucine zipper protein, it regulates the expression of various antioxidant genes that safeguard cells from oxidative stress and damage. While NRF2 activation is beneficial for the survival of normal cells, its overactivation in cancer cells can enhance tumor cell survival, proliferation, and resistance to treatments. Importantly, NRF2 has a dual context-dependent role, functioning as a tumor suppressor when transiently activated in normal cells to prevent carcinogenesis, but as an oncogene when persistently activated in established tumors. Understanding NRF2’s transcriptional alterations and developing targeted therapies could improve cancer management, prognosis and treatment outcomes, making it a promising target for precision oncology. This review aims to provide a comprehensive overview of NRF2 activation in female malignancies, including cervical, endometrial, ovarian, vaginal, vulvar and, breast cancers, and its association with chemoresistance, highlighting challenges and opportunities for developing more effective cancer treatments.
Classification and regulatory interactions of key transcription factors in COVID-19
Modipane, Ndimo; Mbambara, Saidon; Serite, Thato; Sathekge, Mike Machaba; Kgatle, Mankgopo (Frontiers Media, 2025-09-30)
SARS-CoV-2, the virus responsible for COVID-19, interferes with the host’s transcriptional control systems, triggering widespread disruption of immune regulation and metabolic stability. Key transcription factors (TFs), including AHR, NRF2, NF-κB, IRFs, HIF-1α, PARP, STAT3, ATF3, and PPARγ, play crucial roles in inflammation, oxidative stress defence, anti-viral responses, and immunometabolic adaptation. Their activity and interactions are modulated by post-translational modifications (PTMs) such as phosphorylation, SUMOylation, and ubiquitination, which shape COVID-19 progression. Specifically, SUMOylation of PPARγ suppresses NF-κB-driven inflammation, though impairment under severe disease amplifies macrophage activation and cytokine release. NRF2 degradation via KEAP1–CUL3–mediated ubiquitination is manipulated by the virus to deregulate oxidative stress responses, while SARS-CoV-2 also modulates NF-κB activity through ubiquitination of viral proteins (e.g., NSP6, ORF7a). Dynamic crosstalk between AHR and NRF2 further illustrates TF duality in detoxification and inflammation, with SUMOylation potentially influencing nuclear retention and transcriptional precision. This review classifies transcription factors into four functional categories: inflammatory regulators, antiviral response mediators, stress and pathogen response elements, and metabolic modulators. It further examines how PTM–driven crosstalk contributes to immune dysregulation. Targeting these transcriptional networks presents promising therapeutic strategies to mitigate hyperinflammation, rebalance immune responses, and enhance clinical outcomes in COVID-19.
18F-FDG PET/CT for prediction of response in breast cancer
Vorster, Mariza; Sathekge, Mike Machaba (Elsevier, 2026-01)
Breast cancer remains one of the most heterogeneous malignancies, with marked variability in biology, therapeutic sensitivity, and clinical outcomes. As treatment strategies evolve toward individualized approaches, early and accurate assessment of response has become critical for optimizing outcomes and minimizing toxicity. Recent Findings: ¹⁸F-FDG PET/CT provides a biologically grounded, non-invasive measure of tumour metabolism, heterogeneity, and early treatment adaptation. Baseline metrics such as SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG)—reflect proliferative drive and aggressiveness, while early changes (ΔSUV, ΔMTV/TLG after 1–2 cycles) predict pathological complete response (pCR) with high negative predictive value. PET-derived nomograms integrating clinical, molecular, and metabolic data outperform clinicopathologic models alone. Radiomic and artificial-intelligence (AI) analyses further refine prediction by quantifying spatial heterogeneity and enabling subtype-specific modelling. Joint EANM/SNMMI guidelines and NCCN recommendations increasingly endorse ¹⁸F-FDG PET/CT for staging and response monitoring in high-risk or locally advanced disease. ¹⁸F-FDG PET/CT has transitioned from staging to precision-response prediction, particularly in HER2-positive and triple-negative breast cancer. Integration into AI driven nomograms supports adaptive, patient-tailored decisions that minimize toxicity and cost while maximizing benefit. Prospective multicentre validation aligned with EANM/SNMMI/NCCN guidance will consolidate PET’s role in adaptive oncology. HIGHLIGHTS • ¹⁸F-FDG PET/CT enables early, non-invasive prediction of therapy response in breast cancer. • Metabolic parameters (SUVmax, MTV, TLG) and ΔSUV predict pCR and survival across subtypes. • Radiomics and AI enhance prediction by quantifying tumour heterogeneity and resistance. • PET-based nomograms outperform clinicopathologic models for pCR and recurrence prediction.

Browse

Recent Submissions