Research Articles (Nuclear Medicine)

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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.
Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act) : a multicentre, retrospective study
Sathekge, Mike Machaba; Lawal, Ismaheel Opeyemi; Bal, Chandrasekhar; Bruchertseifer, Frank; Ballal, Sajana; Cardaci, Giuseppe; Davis, Cindy; Eiber, Mathias; Hekimsoy, Türkay; Knoesen, Otto; Kratochwil, Clemens; Lenzo, Nat P.; Mahapane, Johncy; Maserumule, Letjie C.; Mdlophane, Amanda H.; Mokoala, Kgomotso M.G.; Ndlovu, Honest; Pant, Vineet; Rathke, Hendrik; Reed, Janet D.; Sen, Ishita B.; Singh, Aviral; Sood, Ashwani; Tauber, Robert; Thakral, Parul; Yadav, Madhav Prasad; Morgenstern, Alfred (Elsevier, 2024-02)
Please read abstract in the article.
Expanding role for gallium-68 PET imaging in oncology
Kleynhans, Janke; Ebenhan, Thomas; Sathekge, Mike Machaba (Elsevier, 2024-11)
Please read abstract in the article.
Co-creation of strategies and interventions to improve mobile-linked point-of-care diagnostics user experience in the South African context : nominal group technique
Nxele, Siphesihle Robin; Moetlhoa, Boitumelo; Dlungwane, Thembelihle; Mathebula, Evans Mantiri; Hlongwana, Khumbulani W.; Dzobo, Matthias; Jaya, Ziningi Nobuhle; Duah, Evans; Kgatle, Mankgopo; Maluleke, Kuhlula; Dlangalala, Thobeka Nomzamo; Marange, Musa; Dzinamarira, Tafadzwa; Thabane, Leha; MMashamba-Thompson, Tivani Phosa (Academic Journals, 2025-06)
User experiences are crucial for the sustainable development and implementation of mobile-linked point-of-care diagnostic technologies. The Nominal Group Technique (NGT) engages stakeholders to co-create strategies that improve the uptake of these technologies in community healthcare settings, particularly in disease-burdened and resource-limited contexts like South Africa. Stakeholders provide insights from social, economic, technological, and medical perspectives. The NGT was used at the REASSURED Diagnostics Symposium workshop, conducted in two phases: identifying potential barriers and developing strategies to address them. Data were collected via Google Forms and thematically analyzed, with themes ranked using a Likert scale from 1 (very low priority) to 7 (highest priority). Key challenges affecting user experiences included psychological issues, turnaround time, and connectivity. Top strategies to mitigate these challenges were health education and offline-capable technology. The NGT workshop facilitated the co-creation of practical strategies to enhance mobile-linked point-of-care diagnostics user experiences in South African healthcare settings.
Efficacy, safety, and patient reported outcomes of rhenium-skin cancer therapy for non-melanoma skin cancer : 1-year results from the EPIC-skin study
Cardaci, Giuseppe; Baxi, Siddhartha; Vohra, Saima; Allison, Cody; Hong, Angela; Mulholland, Nicola; Sathekge, Mike Machaba; Mokoala, Kgomotso M.G.; Heuschkel, Martin; Tietze, Julia; Mirzaei, Siroos; Dahlhoff, Gerhard (Elsevier, 2025-07)
PURPOSE : Rhenium-skin cancer therapy (SCT) is an innovative, noninvasive radionuclide treatment for nonmelanoma skin cancer (NMSC), which is administered in a single outpatient treatment session. A global, multicenter, single-arm, phase 4 post-marketing clinical study was established to evaluate efficacy, safety, cosmesis, and patient-reported outcomes of OncoBeta rhenium-SCT for NMSC. This report details scheduled 12-month interim results, including toxicity, cosmesis, and patient-reported outcomes. METHODS AND MATERIALS : Eligible patients had biopsy-proven stage I or II basal cell carcinoma or squamous cell carcinoma (SCC) lesions ≤3 mm deep and ≤8 cm 2 in area. Patients were administered rhenium-SCT as a resin applied to adhesive foil affixed to the lesion/s, with a dose of 50 Gy to the deepest point. As per the treatment protocol, efficacy was assessed using modified Response Evaluation Criteria in Solid Tumors criteria after 12 months, with planned primary endpoint measuring complete response scheduled for 24 months. Secondary endpoints included patient-reported quality of life (Skin Cancer Index) treatment comfort, cosmesis (visual assessment scale; 1: poor -10: not visible), and toxicity (CTCAE v5.0). RESULTS : Response rates for 185 treated lesions from 140 patients were 94.1% (174/185) complete response, and 3.2% (6/185) partial response. The remaining lesions were classified as progressive or stable disease in 2.2% (4/185) and 0.5% (1/185), respectively. Quality of life improved by a mean 10.55 (95% CI, 3.79, 17.31) points (100-point scale) from baseline. No patients reported pain or discomfort during treatment. Most patients (88%, 129/147) developed radiation dermatitis as expected, which was predominantly grade 1 or 2 in severity and resolved rapidly. The most common 12-month toxicity in patients was grade 1 hypopigmentation (60.4%; 78/129), while there was no incidence of grade 3 or 4 toxicities at this time. Patient- and clinician-reported cosmesis visual assessment scale outcomes were broadly favorable at 8.1 and 7.7, respectively (10-point scale). CONCLUSIONS : This 12-month interim analysis of EPIC-Skin indicates rhenium-SCT is an effective and well-tolerated treatment for shallow basal cell carcinoma and SCC lesions, yielding favorable safety, cosmesis, and patient-satisfaction outcomes. These outcomes underscore the utility of rhenium-SCT as a single-session, noninvasive treatment for NMSC, offering a safe, effective, and efficient alternative to surgery for patients with functional or cosmetic considerations, and/or comorbidities.
Non-FDG hypoxia tracers
Mokoala, Kgomotso M.G.; Sathekge, Mike Machaba (Elsevier, 2024-11)
Hypoxia plays a critical role in tumor biology, influencing cancer progression, treatment resistance, and patient prognosis. While 18-Fluorine fluoredeoxyglucose ([18F]F-FDG) PET imaging has been the standard for metabolic assessment, its limitations in accurately depicting hypoxic tumor regions necessitate the exploration of non-FDG hypoxia tracers. This review aims to evaluate emerging non-FDG radiotracers, such as nitroimidazole derivatives, copper-based agents, gallium-based agents and other innovative compounds, highlighting their mechanisms of action, biodistribution, and clinical applications. We will discuss the advantages and challenges associated with hypoxia imaging, as well as recent advancements in imaging techniques that enhance the assessment of tumor hypoxia. By synthesizing current research, this review seeks to provide insights into the potential of non-FDG hypoxia tracers for improving cancer diagnosis, treatment planning, and monitoring, ultimately contributing to more personalized and effective cancer care.
Visualisation of in vivo protein synthesis during mycobacterial infection through [68Ga]Ga-DOTA-puromycin µPET/MRI
Eigner, Sebastian; Kleynhans, Janke; Vera, Dennis R. Beckford; Sathekge, Mike Machaba; Henke, Katerina Eigner; Ebenhan, Thomas (Nature Research, 2024-08-20)
Radiolabelled puromycin analogues will allow the quantification of protein synthesis through nuclear medicine-based imaging. A particularly useful application could be the non-invasive longitudinal visualisation of mycobacterial activity through direct quantification of puromycin binding. This study assesses the value of [68Ga]Ga-DOTA-puromycin in the visualisation of mycobacteria through positron emission tomography combined with magnetic resonance imaging (µPET/MRI). The radiopharmaceutical was produced by previously published and validated methods. [68Ga]Ga-DOTA-Puromycin imaging was performed on severe immunodeficient mice infected with Bacille Calmette-Guérin-derived M. Bovis (BCG). Acute and chronic infection stages were examined by µPET/MRI. A follow-up group of animals acted as controls (animals bearing S. aureus-derived infection and sterile inflammation) to assess tracer selectivity. [68Ga]Ga-DOTA-puromycin-µPET/MRI images revealed the acute, widespread infection within the right upper shoulder and armpit. Also, [68Ga]Ga-DOTA-puromycin signal sensitivity measured after a 12-week period was lower than that of [18F]FDG-PET in the same animals. A suitable correlation between normalised uptake values (NUV) and gold standard histopathological analysis confirms accurate tracer accumulation in viable bacteria. The radiopharmaceutical showed infection selectivity over inflammation but accumulated in both M. Bovis and S. Aureus, lacking pathogen specificity. Overall, [68Ga]Ga-DOTA-puromycin exhibits potential as a tool for non-invasive protein synthesis visualization, albeit without pathogen selectivity.
Gallium-68-NODASA-functionalized D-lysine radiosynthesis and first-line in vitro characterization-a potential PET imaging agent for infection
Gouws, Christiaan A.; Naicker, Tricia; Duvenhage, Janie; De la Torre, Beatriz G.; Albericio, Fernando; Kruger, Hendrik G.; Marjanovic-Painter, Biljana; Mdanda, Sipho; Zeevaart, Jan Rijn; Ebenhan, Thomas; Govender, Thavendran (South African Chemical Institute, 2025-03)
The advancement of new Positron Emission Tomography (PET) radiotracers for differentiating bacterial infections from sterile inflammation is essential for accurate diagnosis and treatment monitoring. D-amino acid-based probes have shown promise for bacterial imaging due to their selective peptidoglycan incorporation. However, host enzyme-mediated racemization of radiolabeled D-amino acids and limited tissue penetration of fluorescence signal of fluorescent D-amino acids limits their in vivo performance. Herein, we report the successful chemical synthesis, optimized radiosynthesis, and the required first-line in vitro characterization of [68Ga]Ga-NDL-1 (NDL = NODASA D-lysine; NODASA = 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid) (the L-isomeric compound, aka. [68Ga]Ga-NLL-1 was evaluated in parallel as the control). Robust radiolabeling was achieved within 60 minutes using the optimized radiolabeling method, featuring the consistent production of very good radiochemical yields (81.7 ± 3.2%), apparent molar activities (17.1 ± 0.8 GBq/μmol) and with excellent radiochemical purities (97.7 ± 0.5%), free of 68Ga-colloids; therefore, deemed suitable for future intravenous administration and micro-PET imaging applications. [68Ga]Ga-NDL-1 was highly stable during prolonged incubation in the presence of 1000-times excess of EDTA (>93%) as well as a during a 2-hour exposure to plasma (>97%). [68Ga]Ga-NLL-1 and [68Ga]Ga-NDL-1 showed minimal overall blood cell binding (<12%) or plasma protein binding (<15%). Results justify further investigation of [68Ga]Ga-NDL-1 as a potential PET imaging agent of infection.
Optimizing theranostics chatbots with context-augmented large language models
Koller, Pia; Clement, Christoph; Van Eijk, Albert; Seifert, Robert; Zhang, Jingjing; Prenosil, George; Sathekge, Mike Machaba; Herrmann, Ken; Baum, Richard; Weber, Wolfgang A.; Rominger, Axel; Shi, Kuangyu (Ivyspring International Publisher, 2025-04)
IINTRODUCTION : Nuclear medicine theranostics is rapidly emerging, as an interdisciplinary therapy option with multi-dimensional considerations. Healthcare Professionals do not have the time to do in depth research on every therapy option. Personalized Chatbots might help to educate them. Chatbots using Large Language Models (LLMs), such as ChatGPT, are gaining interest addressing these challenges. However, chatbot performances often fall short in specific domains, which is critical in healthcare applications. METHODS : This study develops a framework to examine the use of contextual augmentation to improve the performance of medical theranostic chatbots to create the first theranostic chatbot. Contextual augmentation involves providing additional relevant information to LLMs to improve their responses. We evaluate five state-of-the-art LLMs on questions translated into English and German. We compare answers generated with and without contextual augmentation, where the LLMs access pre-selected research papers via Retrieval Augmented Generation (RAG). We are using two RAG techniques: Naïve RAG and Advanced RAG. RESULTS : A user study and LLM-based evaluation assess answer quality across different metrics. Results show that Advanced RAG techniques considerably enhance LLM performance. Among the models, the best-performing variants are CLAUDE 3 OPUS and GPT-4O. These models consistently achieve the highest scores, indicating robust integration and utilization of contextual information. The most notable improvements between Naive RAG and Advanced RAG are observed in the GEMINI 1.5 and COMMAND R+ variants. CONCLUSION : This study demonstrates that contextual augmentation addresses the complexities inherent in theranostics. Despite promising results, key limitations include the biased selection of questions focusing primarily on PRRT, the need for comprehensive context documents. Future research should include a broader range of theranostics questions, explore additional RAG methods and aim to compare human and LLM evaluations more directly to enhance LLM performance further.

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