Research Articles (Nuclear Medicine)

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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.
Advancements in renal imaging : a comprehensive systematic review of PET probes for enhanced GFR and renal perfusion assessment
Abdulrahman , Marwah; Abdlkadir, Ahmed Saad; Moghrabi, Serin; Alyazjeen, Salem; Al-Qasem, Soud; Sweedat, Deya’ Aldeen Sulaiman; Ruzzeh, Saad; Stanimirovi´c, Dragi; Kreissl, Michael C.; Shi, Hongcheng; Sathekge, Mike Machaba; Al-Ibraheem, Akram (MDPI, 2025-12)
Glomerular filtration rate (GFR) is a key indicator of renal function. Traditional methods for GFR measurement have limitations including invasiveness, low spatial resolution, and lengthy protocols. Positron emission tomography (PET) radiotracers have emerged as promising tools for non-invasive, accurate, and dynamic renal function assessment. OBJECTIVES : This systematic literature review evaluates the clinical utility, and current evidence surrounding PET radiotracers used for GFR measurement in humans, emphasizing advances over conventional renal imaging modalities. METHODS : A systematic literature search was conducted in PubMed, Web of Science, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, from database inception to November 2024. The search identified studies evaluating PET-based measurement of glomerular filtration rate (GFR) and renal perfusion. Inclusion criteria encompassed human studies using PET radiotracers (e.g., 68Ga, 18F) with comparisons to reference standards (estimated GFR or serum creatinine). Two authors independently screened titles/abstracts, extracted data, and assessed bias using Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Exclusions included animal studies, reviews, and non-English articles. RESULTS : Eleven studies met inclusion criteria, with 68Ga-EDTA showing the highest validation against reference standards such as 51Cr-EDTA plasma clearance, demonstrating strong correlation. PET imaging offered superior spatial–temporal resolution, enabling accurate split renal function assessment and quantitative analysis of both filtration and perfusion. 68Ga-somatostatin analogues exhibited moderate correlations between renal SUV and estimated GFR, with post-PRRT uptake changes indicating early nephrotoxicity. Among novel tracers, 68Ga-FAPI showed a strong inverse SUV–GFR relationship, reflecting renal fibrosis and suggesting potential as a chronic kidney disease (CKD) biomarker but requires further clinical validation. Limitations across studies include small sample sizes, retrospective designs, and variability in reference standards. CONCLUSIONS : PET radiotracers, particularly 68Ga-EDTA, represent a significant advancement for non-invasive, quantitative GFR measurement with improved precision and renal anatomical detail compared to traditional methods. Future prospective, large-scale human studies with standardized protocols are needed to establish these PET tracers as routine clinical tools in nephrology. Integration of hybrid PET/MRI and novel tracer development may further enhance renal diagnostic capabilities.
The current status of nuclear medicine in Africa
Brink, Anita; Kleynhans, Janke; Grigoryan, Anna; Omar, Walid; Mekonnen, Bethlehem W.; Kolade, Olumayowa U.; Mokoala, Kgomotso M.G.; Sangiwa, Bright A.; Hashford, Francis; Nagaraj, Harish; Sakr, Tamer M.; Bentaleb, Naoual; Giammarile, Francesco; Estrada-Lobato, Enrique; Elrefaei, Amal; Knoll, Peter; Korde, Aruna; Paez, Diana (Society of Nuclear Medicine and Molecular Imaging, 2026-02)
Please read abstract in the article.
Clinical image-based dosimetry of Actinium-225 in targeted alpha therapy
Ramonaheng, Kamo; Banda, Kaluzi; Qebetu, Milani; Goorhoo, Pryaska; Legodi, Khomotso; Masogo, Tshegofatso; Seebarruth, Yashna; Mdanda, Sipho; Sibiya, Sandile; Mzizi, Yonwaba; Davis, Cindy; Smith, Liani; Ndlovu, Honest; Kabunda, Joseph; Maes, Alex; Van de Wiele, Christophe; Al-Ibraheem, Akram; Sathekge, Mike Machaba (MDPI, 2026-01)
Please read abstract in the article.
The impact of fire drills on firefighters’ performance
Ramohale, Matome R.; Mokaleng, Botshelo B.; Monnye, Nthai (AOSIS, 2025-04-30)
Firefighting is one of the most physically demanding, dangerous, and stressful jobs, constituting several physical activities, which include moving equipment up the stairs in tall buildings and deploying charged hoses. In fire management, structured training exercises are fire drills used to prepare staff for successful responses to fires situations. Firefighters, emergency responders, and other pertinent people can practice responding to a real fire by simulating real-life fire events. However, South African fire departments and stations, particularly in Mpumalanga, Nkangala district, are failing to comply with the regulations because they are not conducting these fire drills once a month. This failure to conduct fire drills has resulted in the loss of skills and knowledge. Poor service delivery has become the norm and prevalent. This study aimed to investigate if fire drills can improve the operational efficacy and psychological state of firefighters. The study adopted a quantitative research approach and collected data from randomly sampled participants who work at fire stations located in Nkangala district in Mpumalanga province in South Africa. The Wilcoxon signed-rank statistical test revealed that fire drills do improve operational efficacy and the psychological state of firefighters, demonstrating that fire drills are a key component of fire department’s performance. This study recommends that fire drills must be mandatory for fire departments in South Africa. CONTRIBUTION : The study’s findings showed that fire exercises enhance firefighters’ performance and have a favourable effect on their mental health.
Targeted alpha therapy in prostate cancer : review of available agents in clinical practice
Ndlovu, Honest; Lawal, Ismaheel Opeyemi; Kabunda, Joseph; Kaoma, Chimbabantu; Mashigoane, Kgomotso; Knoesen, Zane; Ramonaheng, Keamogetswe; Sibiya, Sandile; Mdlophane, Amanda H.; Mdanda, Sipho; Ebenhan, Thomas; Kgatle, Mankgopo; Zeevaart, Jan Rijn; Mokoala, Kgomotso M.G.; Al-Ibraheem, Akran; Sathekge, Mike Machaba (Edizioni Minerva Medica, 2025-06)
Targeted alpha therapy (TAT) has shown promise in prostate cancer patients, both hormone-sensitive and castration-resistant, with or without prior treatment. TAT's radiobiological properties explain why it is more potent than other forms of ionizing radiation, such as the clinically approved [177Lu]Lu-PSMA-617. Although most TAT agents used in compassionate care or clinical trials target the prostate-specific membrane antigen (PSMA), some alternatives are yet to be used clinically, some of which aim to address PSMA-negative prostate cancer. These include [223Ra]RaCl2, which is approved for palliative bone pain, and a variety of other non-PSMA antigen or receptor-targeting medicines. Whereas this study focuses on TAT medicines that are currently available for clinical use, it also explores these preclinical agents.
The advent of Astatine-211 in targeted radionuclide therapy in prostate cancer : will it come to true fruition?
Hlongwa, Khanyisile N.; Rivombe, Prudence M.; More, Stuart (Edizioni Minerva Medica, 2025-06)
With the growth and surge of prostate cancer theranostics globally, multiple targeted radionuclide therapy (TRT) agents have been utilized to aim to provide a tumoricidal effect to patients who would benefit from TRT. Despite the fact that approved isotopes such as Strontium-89, Samarium-153 and Radium-223 exist, Lutetium-177 prostate specific membrane antigen (PSMA) has revolutionized the impact of radioligand therapy (RLT) in this domain. Key defining clinical trials such as the VISION, TheraP and PSMAfore trials have given clear evidence of the benefit of PSMA RLT in the treatment landscape of metastatic castrate resistant prostate cancer. A number of other radioisotopes in the PSMA RLT domain have also more recently come into the field, notably Terbium-161, Copper- 67 and Iodine-131. Targeted Alpha Therapy (TAT) has grown significantly as well over the last few years owing to physical properties of its high linear energy transfer and DNA damage provided by alpha particles in comparison to beta particles. Actinium-225 PSMA based TAT has formed the basis of prostate cancer theranostics since its initial application, however, many other alpha isotopes are being explored owing to some of the side effects that Actinium-225 presents. Astatine-211, owing to its shorter half-life, has become a more attractive option for its potential utilization in prostate cancer theranostics. Whilst there is preclinical work detailing its efficacy in suppressing tumor growth and limited toxicity profiles, translation into humans is still in its infancy and requires further exploration. A number of clinical trials have utilized Astatine-211 in other malignancies with virtually no work related to prostate cancer. Moreover, the logistics and infrastructure required to support global efforts to make Astatine-211 more readily available should be high on the agenda as well. This narrative review of the literature aims to showcase the current status of Astatine-211 efforts in prostate cancer care with available data (including clinical trials).
Cost-cutting at the expense of care and training : the predictable consequences of attempts at austerity by the Gauteng Department of Health
Senkubuge, Flavia; Soma-Pillay, Priya; Basu, Debashis; Madhi, Shabir; Motara, Feroza; Lekgwara, Patrick; Motloba, Pagollang; Vangu, Willy; Nodikida, Mzulungile; Madini, Simon; Sathekge, Mike Machaba; Ncube, Mhlengi; Chauke, Lawrence; Botha, Ruhann; Ledibane, Tladi; Coovadia, Ashraf; Dhlodhlo, Ndlela; Holland, Shakeera; Sihlangu, Cedric; Bayat, Zaheer; Chauke, Risenga; Oosthuizen, William; Mbodi, Langanani (South african Medical Association, 2025-04)
The Gauteng Department of Health (GDoH) has recently initiated drastic austerity measures, including the unilateral downgrading of commuted overtime (COT) tiers, the termination of sessional contracts, and non-filling of posts following resignations and retirement. These actions were taken without meaningful engagement with affected stakeholders, and have sent shockwaves through Gauteng Province’s public healthcare system. At stake are not only overtime contracts and working hours, but the very foundations of patient care, professional training for medical students and specialist training, and the future sustainability of healthcare delivery in South Africa (SA)’s most populous province.
Advances in dosimetry and imaging for 203Pb and 212Pb radiotheranostics
Ramonaheng, Keamogetswe; Qebetu, Milani; Banda, Kaluzi; Goorhoo, Pryaska; Legodi, Khomotso; Mdanda, Sipho; Sibiya, Sandile; Mzizi, Yonwaba; Ndlovu, Honest; Kabunda, Joseph; Yang, Mengdie; Shi, Kuangyu; Sathekge, Mike Machaba (Elsevier, 2025-11)
Targeted alpha therapy (TAT) with 212Pb is rapidly emerging as a potent modality for cancer treatment due to the high linear energy transfer and short path length of α-particles, which enable precise tumor cell killing while sparing surrounding healthy tissue. Its elementally identical theranostic partner, 203Pb, functions as a γ-emitting surrogate for quantitative SPECT imaging, providing essential information for patient-specific dosimetry and treatment planning. Advances in SPECT imaging, ranging from NaI(Tl)-based dual-head systems to CZT multi-detector gamma cameras, have enhanced spatial resolution, quantitative accuracy, and lesion detectability, enabling rapid patient scanning and improved activity quantification for dosimetry. Clinical dosimetry workflows that integrate serial 203Pb SPECT/CT acquisitions, pharmacokinetic modeling, and image-based activity quantification facilitate reliable generation of time–activity curves and absorbed dose estimates. Organ-level and voxel-based dosimetry, combined with advanced reconstruction and microdosimetric modeling, further refine dose calculations, supporting individualized therapy planning. Collectively, these developments highlight the translational potential of the 203Pb/212Pb theranostic pair. The aim of this review is to provide a comprehensive assessment of 212Pb-TAT, encompassing clinical applications, surrogate imaging with 203Pb, gamma camera performance, dosimetry workflows, and predictive activity quantification, illustrating how these advances collectively enable quantitative, patient-specific, and theranostic-integrated radionuclide therapy.
Implementation of radiotheranostics : challenges, barriers, and IAEA-driven strategies for sustainable access
Al-Ibraheem, Akram; Brink, Anita; Lee, Sze Ting; De Los Reyes, Amelia; Paez, Diana; Craviolatti, Pietro Selemo; Llamas-Olier, Augusto; Giammarile, Francesco; Abdlkadir, Ahmed S.; Estrada-Lobato, Enrique; Abdel-Wahab, May; Prior, John; Scott, Andrew M.; Sathekge, Mike Machaba (Elsevier, 2025-11)
Radiotheranostics represent a cutting-edge advancement in the management of noncommunicable diseases, integrating diagnostic imaging with targeted radiotherapy in a single, personalized approach. Over the past decade, the field has gained substantial momentum, with several radiopharmaceuticals now incorporated into clinical practice, most notably for neuroendocrine tumors and prostate cancer. The pipeline of novel agents continues to grow, offering promising therapeutic options for patients with cancers resistant to conventional therapies. Despite these advances, the broad implementation of radiotheranostics is impeded by several challenges, including logistical constraints, financial limitations, resource scarcity, political instability, and regulatory and educational barriers. Overcoming these obstacles requires coordinated mitigation strategies focused on strengthening education and training, expanding radiopharmaceutical production and development, enhancing research capacity, and establishing robust quality management systems. This review provides a comprehensive overview of the current global landscape of radiotheranostics, identifies key implementation barriers, and offers expert-driven strategies and recommendations from the International Atomic Energy Agency to support sustainable and equitable access to radiotheranostics.
Alpha therapies : where and when is the future in neuroendocrine tumours?
Vorster, Mariza; Grana, Chiara Maria; Travascio, Laura; Sathekge, Mike Machaba (Springer, 2025-08)
Neuroendocrine tumors (NETs) represent a diverse group of neoplasms arising from neuroendocrine cells, treatable with various modalities including targeted radionuclide therapy. Traditional treatments such as surgery, somatostatin analogues, chemotherapy, target therapies and peptide receptor radionuclide therapy (PRRT) with beta-emitting isotopes like 177Lu-DOTATATE have shown good clinical efficacy. However, 177Lu-DOTATATE may be less effective in refractory or progressive cases, necessitating the transition to alpha-emitting therapies. The emergence of alpha therapies, leveraging the potent cytotoxicity of alpha-emitting isotopes, signifies a notable advancement in the therapeutic landscape for NETs. This review aims to provide an overview of the most significant developments and evidence for the use of targeted alpha therapies in neuroendocrine tumors. Alpha particles, with their high linear energy transfer (LET) and short range, offer distinct advantages over beta particles. Their potent cytotoxicity can cause double-strand DNA breaks, leading to higher tumor cell kill rates. Several alpha-emitting isotopes, including Actinium-225, Bismuth-213, and Lead-212, are currently being investigated for their therapeutic potential in NETs. These isotopes deliver lethal radiation doses to tumor cells while minimizing collateral damage to healthy tissues, even more targeted in hepatic disease when intraarterial administration is feasible. Despite challenges related to Ac-225 production, availability, costs, dosimetry, standardization, and sufficient long-term follow-up data, the clinical success in treating resistant and aggressive forms of NETs underscores the need for increased investment and research to optimize production and distribution processes. Developing reliable supply chains and comprehending the potential long-term effects of alpha emitters are essential steps. The time for Targeted Alpha Therapies is undeniably here and now, with continued advancements holding the potential to revolutionize the treatment of neuroendocrine tumors, providing hope and improved outcomes for patients globally.
Synthesis and characterisation of DOTA-kisspeptin-10 as a potential gallium-68/lutetium-177 pan-tumour radiopharmaceutical
Kleynhans, Janke; Reeve, Robert; Driver, Cathryn Helena Stanford; Marjanovic-Painter, Biljana; Sathekge, Mike Machaba; Zeevaart, Jan Rijn; Ebenhan, Thomas; Millar, Robert P. (Wiley, 2025-03)
Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. A gallium-68 labelled kisspeptin-10 (KP10), the minimal biologically active structure, has potential as a pan-tumour radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was attached to the NH2-terminus of KP10 as we posited from our previous publications that this modification would not impair biological activity. Here, we showed that the biological activity, as monitored by stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene, was indeed similar for KP10 and DOTA-KP10. The optimisation of radiolabelling with gallium-68 and lutetium-177 is described. Stability in serum, plasma and whole blood was also investigated. Pharmacokinetics and biodistribution were established with micro-PET/CT (positron emission tomography/computerised tomography) and ex vivo measurements. Dynamic studies with micro-PET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 min. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These results lay the foundation for the further development of DOTA-KP10 analogues that have high binding affinity along with proteolytic resistance.
The role of pioneering transcription factors, chromatin accessibility and epigenetic reprogramming in oncogenic viruses
Kgatle, Mankgopo; Mbambara, Saidon; Khoza, Leon; Fadebi, Olalekan; Mashamba-Thompson, Tivani Phosa; Sathekge, Mike Machaba (Frontiers Media, 2025-06-16)
Oncogenic viruses typically manipulate host cellular mechanisms to drive tumorigenesis. They exploit pioneering transcription factors to modify gene expression, enabling uncontrolled proliferation. These viruses alter chromatin accessibility and induce chromatin remodelling, disrupting DNA repair and promoting viral genome integration. Additionally, epigenetic reprogramming through mechanisms like DNA methylation and histone modifications silences tumor suppressor genes and activates oncogenes. Understanding these mechanisms is critical for identifying more improved therapeutic targets, improving diagnostics, and predicting disease progression. Advances in this field can guide the development of innovative treatments and early detection tools. This comprehensive review synthesizes existing knowledge on the contributions of oncogenic viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and human T-cell leukaemia virus type 1 (HTLV-1), Epstein–Barr virus (EBV), human herpesvirus 8 (HHV-8), and Merkel cell polyomavirus (MCV) to cancer development, highlighting their therapeutic relevance and driving forward research in viral oncogenesis.
Consensus nomenclature for radionuclide therapy : initial recommendations from nuclear medicine global initiative
Al-Ibraheem, Akram; Scott-, Andrew M.; Abdlkadir, Ahmed Saad; Vrachimis, Alexis; Lamoureux, Francois; Trujillo, Patricia Bernal; Bailey, Dale L.; More, Stuart; Giammarile, Francesco; Kumar, Rakesh; Nonnekens, Julie; Cutler, Cathy S.; Urbain, Jean-Luc C.; Dibble, Elizabeth H.; Sathekge, Mike Machaba; Bomanji, Jamshed; Cerci, Juliano J.; Thomas, Elizabeth; Small, William; Louw, Lizette; Hyun, O. Joo; Lee, Sze Ting; Nadel, Helen; Jacene, Heather; Watabe, Tadashi; Bom, Henry Hee-Seung; Bouyoucef, Salah Eddine; Weston, Charlotte; Wadsley, Jonathan; Irwin, Andy G.; Croasdale, Jilly; Zanzonico, Pat; Paez, Diana; Ghesani, Munir (Society of Nuclear Medicine and Molecular Imaging, 2025-05)
Since its inception in 2012, the Nuclear Medicine Global Initiative (NMGI) of the Society of Nuclear Medicine and Molecular Imaging has played an important role in addressing significant challenges in the field of nuclear medicine and molecular imaging. The first 3 projects were dedicated to standardizing pediatric nuclear medicine practices, addressing the global challenges of radionuclide access and availability, and assessing the educational and training initiatives on theranostics across the globe. These efforts aimed to advance human health, foster worldwide educational collaboration, and standardize procedural guidelines to enhance quality and safety in nuclear medicine practice. In its latest project, NMGI aimed to develop a unified nomenclature for systemic radionuclide therapy in nuclear medicine, addressing the diverse terminology currently used. An online survey was distributed to NMGI member organizations, drawing participation from various geographical locations and disciplines. The survey anonymously collected responses from physicians, physicists, scientists, radiopharmacists, radiopharmaceutical scientists, dosimetrists, technologists, and nurse managers, totaling 240 responses from 30 countries. Findings revealed a prevailing use of the term targeted radionuclide therapy for radionuclide therapy, with 52% of respondents expressing a preference for this term. In contrast, approximately 37% favored “radiopharmaceutical therapy,” whereas 11% favored “molecular radionuclide therapy.” Other key terms under the umbrella of targeted radionuclide therapy were also discussed to achieve a consensus on terminology. NMGI efforts to standardize terminology in this dynamic and fluid field should improve communication within the field, better reflect the technology used, enable comparison of results, and ultimately lead to improved patient outcomes.
Diuresis during 18F-flotufolastat (rhPSMA-7.3) PET/CT improves recurrence detection after prostatectomy : a prospective Phase II trial
Lawal, Ismaheel Opeyemi; Mushtaq, Aliza; Jani, Ashesh B.; Rupji, Manali; Dhere, Vishal R.; Patel, Sagar A.; Bilen, Mehmet A.; Patel, Pretesh R.; Sebastian, Nikhil T.; Switchenko, Jeffrey M.; Schuster, David M.; Marcus, Charles (Society of Nuclear Medicine and Molecular Imaging, 2025-02)
Please read abstract in the article.
Radiolabeled antibody–drug conjugates in the treatment of solid tumors
Lawal, Ismaheel Opeyemi; Abubakar, Sofiullah O.; Ndlovu, Honest; Ismaila, Aisha; Sathekge, Mike Machaba (Elsevier, 2025-11)
Antibody-drug conjugates (ADCs) utilize monoclonal antibodies (mAbs) that target tumor-specific antigens to deliver potent cytotoxic chemotherapy payloads to the tumor, while sparing normal tissues. The chemotherapy agents employed in ADCs are very potent, causing a tumoricidal effect at low drug concentrations. Several ADCs have been approved for the treatment of different solid tumors over the last decade following the superior efficacy and safety they demonstrated above standard-of-care treatment modalities in several clinical trials. Despite their efficacy, some patients do not respond to treatment with ADCs, as objective response rate typically range from 30% to 50%, and as low as 20% in some instances. Some patients who initially respond to treatment develop acquired resistance during their treatment, necessitating strategies to improve response rates and overcome treatment resistance. Radiation from radionuclides, with their ability to evoke a synergistic antitumor effect when used in combination with cytotoxic chemotherapy and induce a tumoricidal effect in tumor cells remote from the tumor they are bound to (crossfire effect), has the potential to improve the outcomes of ADC treatment. An expanding body of evidence, reporting the successful radiolabeling of established and experimental ADCs, is emerging in the literature. These studies have demonstrated improved antitumor effect of radiolabeled ADC relative to cold ADC, paving the way for further exploration, including in clinical settings.
Prostate-specific membrane antigen : alpha-labeled radiopharmaceuticals
Ndlovu, Honest; Mokoala, Kgomotso M.G.; Lawal, Ismaheel Opeyemi; Emmett, Louise; Sathekge, Mike Machaba (Elsevier, 2024-07)
Novel prostate-specific membrane antigen (PSMA) ligands labeled with α-emitting radionuclides are sparking a growing interest in prostate cancer treatment. These targeted alpha therapies (TATs) have attractive physical properties that deem them effective in progressive metastatic castrate-resistant prostate cancer (mCRPC). Among the PSMA TAT radiopharmaceuticals, [225Ac]Ac-PSMA has been used extensively on a compassionate basis and is currently undergoing phase I trials. Notably, TAT has the potential to improve quality of life and has favorable antitumor activity and outcomes in multiple scenarios other than in mCRPC. In addition, resistance mechanisms to TAT may be amenable to combination therapies. KEY POINTS • The physical characteristics of α-particles allow for the better radiobiological efficiency of prostate-specific membrane antigen radiopharmaceuticals that emit α-particles. They have a position in the progressive metastatic castrate-resistant prostate cancer because of their direct and indirect cytotoxic effects on DNA and organelles through reactive oxygen species, bystander, and abscopal immune-mediated pathways. • Whether the metastatic prostate cancer is hormone-sensitive or castration-resistant, targeted-alpha therapy (TAT) has shown strong antitumor effectiveness, long-term survival, and an improvement in quality of life in patients at different stages of the disease. • The salivary glands are the dose-limiting organs. Salivary gland toxicity secondary to TAT may manifest with indirect clinical symptoms such as loss of appetite impacting on the quality of life. Various mitigatory measures have been partially effective in reducing its incidence.

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