Akram Al-Ibraheem, Anita Brink, Sze Ting Lee, Amelia De Los Reyes, Diana Paez, Pietro Selemo Craviolatti, Augusto Llamas Olier, Francesco Giammarile, Ahmed S Abdlkadir, Enrique Estrada-Lobato, May Abdel-Wahab, John Prior, Andrew M Scott, Mike Machaba Sathekge
{"title":"Implementation of Radiotheranostics: Challenges, Barriers, and IAEA-Driven Strategies for Sustainable Access.","authors":"Akram Al-Ibraheem, Anita Brink, Sze Ting Lee, Amelia De Los Reyes, Diana Paez, Pietro Selemo Craviolatti, Augusto Llamas Olier, Francesco Giammarile, Ahmed S Abdlkadir, Enrique Estrada-Lobato, May Abdel-Wahab, John Prior, Andrew M Scott, Mike Machaba Sathekge","doi":"10.1053/j.semnuclmed.2025.07.005","DOIUrl":"https://doi.org/10.1053/j.semnuclmed.2025.07.005","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aurélien Callaud, Heying Duan, Elif Hindié, Clément Morgat, Andrei Iagaru
{"title":"GRPR Expression in Metastatic Cancers: A Review of Potential Application of GRPR-Radioligand Therapy.","authors":"Aurélien Callaud, Heying Duan, Elif Hindié, Clément Morgat, Andrei Iagaru","doi":"10.1053/j.semnuclmed.2025.07.003","DOIUrl":"https://doi.org/10.1053/j.semnuclmed.2025.07.003","url":null,"abstract":"<p><p>Gastrin-Releasing Peptide Receptor (GRPR) represents a promising molecular target for radionuclide therapy (TRT) across a variety of malignancies due to its overexpression in several tumor types, including prostate, breast, lung, melanoma, cervix, neuroblastoma, head and neck, and colon cancers. While expression patterns vary-with high GRPR expression notably observed in cervix and neuroblastoma cancers-tumor heterogeneity and metastatic profiles remain challenges for patient selection and therapy optimization. Recent advances in GRPR-targeted radiopharmaceutical development have focused on overcoming peptide instability and enhancing tumor uptake, exemplified by novel compounds such as AMTG with improved proteolytic resistance and albumin binding domains to extend circulatory half-life. Furthermore, innovative radionuclides like terbium-161, lead-212, copper-67, cobalt-58 m, and arsenic-77 offer enhanced therapeutic potential beyond the current standard of lutetium-177 through favorable decay characteristics including Auger electron emission and alpha-particle therapy. Preclinical and early clinical studies demonstrate encouraging tumor targeting and therapeutic efficacy with manageable toxicity profiles, particularly in prostate and cervix cancers. However, further investigation into GRPR expression heterogeneity, metastatic distribution, and safety is necessary to refine patient stratification and maximize clinical benefit. This evolving landscape positions GRPR-TRT as a versatile and potent approach, with the potential to expand targeted radionuclide therapy to a broader range of malignancies and improve outcomes in advanced cancers with limited treatment options.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of [177Lu] Lu-Satoreotide Tetraxetan in Somatostatin Receptor-Positive Neuroendocrine Tumors.","authors":"Kalyan Mansukhbhai Shekhda, Shaunak Navalkissoor","doi":"10.1053/j.semnuclmed.2025.07.002","DOIUrl":"https://doi.org/10.1053/j.semnuclmed.2025.07.002","url":null,"abstract":"<p><p>Peptide receptor radionuclide therapy (PRRT) targeting the somatostatin receptor with receptor agonists has emerged as a key treatment in the management of well-differentiated neuroendocrine tumors (NETs). The therapeutic efficacy of these agents has traditionally been attributed to receptor-mediated internalization of the radiolabeled peptide into tumor cells. In contrast, somatostatin receptor (SSTR) antagonists bind to the receptor without undergoing significant internalization. Despite this theoretical limitation, accumulating preclinical and clinical evidence supports the therapeutic utility of SSTR antagonists. These agents have been shown to bind to a greater number of receptor sites and exhibit prolonged tumor retention, properties that may enhance both imaging sensitivity and therapeutic efficacy. Among the antagonists studied, [¹⁷⁷Lu]Lu-satoreotide tetraxetan is the most extensively investigated to date. In this article, we review both preclinical and clinical data evaluating the efficacy and safety of [¹⁷⁷Lu]Lu-satoreotide tetraxetan in the treatment of neuroendocrine tumors. We also provide a brief overview of other SSTR antagonists currently under investigation.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter from the Editors","authors":"Kirsten Bouchelouche, M. Michael Sathekge","doi":"10.1053/j.semnuclmed.2025.07.004","DOIUrl":"10.1053/j.semnuclmed.2025.07.004","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 645-647"},"PeriodicalIF":5.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Honest Ndlovu , Ismaheel O. Lawal , Kgomotso M.G. Mokoala , Sipho Mdanda , Mike M. Sathekge
{"title":"New Promising Targets for Imaging in Infection","authors":"Honest Ndlovu , Ismaheel O. Lawal , Kgomotso M.G. Mokoala , Sipho Mdanda , Mike M. Sathekge","doi":"10.1053/j.semnuclmed.2025.06.013","DOIUrl":"10.1053/j.semnuclmed.2025.06.013","url":null,"abstract":"<div><div>The diagnosis of infection is crucial in-patient survival, prevention of prolonged hospitalization and undue morbidity and mortality. This can be achieved using various tools target at the specific microbes or the host immune response components. The most useful tool will be one that diagnoses the specific causative microbe by being able to distinguish sterile inflammation from infection which by itself causes inflammation. This allows timeous institution of the appropriate and effective antimicrobial therapy, effectively reducing the incidence of antimicrobial resistance. Current standard of care diagnostic tools such as inflammatory markers, culture, morphological imaging and molecular imaging tools has specific shortcomings which necessities enlist other tools to complement them. Various targets for infection imaging have been explored and demonstrated variable utilities in the preclinical or clinical settings. This review will discuss the relevant targets in bacteria, fungi and viruses and delve into the promising or novel molecular imaging tools.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 804-811"},"PeriodicalIF":5.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nozipho Nyakale , Alex Maes , Mike Sathekge , Shaobo Li , Justine Maes , Christophe Van de Wiele
{"title":"PSMA-Targeted Positron Emission Tomography Imaging in Solid Tumors Other Than Prostate Carcinoma: An Update","authors":"Nozipho Nyakale , Alex Maes , Mike Sathekge , Shaobo Li , Justine Maes , Christophe Van de Wiele","doi":"10.1053/j.semnuclmed.2025.06.006","DOIUrl":"10.1053/j.semnuclmed.2025.06.006","url":null,"abstract":"<div><div>Prostate-specific membrane antigen (PSMA) has been previously shown to be over-expressed on newly formed vessels of a wide variety of solid tumors other than prostate carcinoma. Accordingly, the potential role of PSMA-targeted positron emitting tomography for staging, restaging and prediction of response to PSMA-targeted treatment modalities, including <sup>177</sup>Lu-PSMA-617, in other solid tumor types is being explored. Results derived from currently available studies on the role of PSMA-targeted imaging in solid tumors other than prostate carcinoma are encouraging with amongst others evidence of improved diagnostic accuracy in patients suffering from clear cell renal cell carcinoma and adenoid cystic adenocarcinoma of the salivary gland when compared to standard of care imaging, leading to a change in patient management in a significant number of patients. Furthermore, in hepatocellular carcinoma and glioblastoma, the comparable diagnostic accuracy of PSMA-targeted PET imaging when compared to contrast-enhanced CT and MRI suggest a potential use of PSMA-targeted PET when findings derived from morphological imaging are doubtful. Also, high PSMA-targeted PET-ligand uptake has been identified in iodine refractory thyroid carcinoma lesions as well as in triple negative breast carcinoma, suggesting a potential role for PSMA-targeted therapy in these patient populations. Thus far published results warrant, however, confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 672-679"},"PeriodicalIF":5.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alireza Safarian , Seyed Ali Mirshahvalad , Abolfazl Farbod , Theresa Jung , Hadi Nasrollahi , Gregor Schweighofer-Zwink , Gundula Rendl , Christian Pirich , Reza Vali , Mohsen Beheshti
{"title":"Artificial Intelligence for Tumor [18F]FDG PET Imaging: Advancements and Future Trends - Part II","authors":"Alireza Safarian , Seyed Ali Mirshahvalad , Abolfazl Farbod , Theresa Jung , Hadi Nasrollahi , Gregor Schweighofer-Zwink , Gundula Rendl , Christian Pirich , Reza Vali , Mohsen Beheshti","doi":"10.1053/j.semnuclmed.2025.06.012","DOIUrl":"10.1053/j.semnuclmed.2025.06.012","url":null,"abstract":"<div><div>The integration of artificial intelligence (AI) into [<sup>18</sup>F]FDG PET/CT imaging continues to expand, offering new opportunities for more precise, consistent, and personalized oncologic evaluations. Building on the foundation established in Part I, this second part explores AI-driven innovations across a broader range of malignancies, including hematological, genitourinary, melanoma, and central nervous system tumors as well applications of AI in pediatric oncology.</div><div>Radiomics and machine learning algorithms are being explored for their ability to enhance diagnostic accuracy, reduce interobserver variability, and inform complex clinical decision-making, such as identifying patients with refractory lymphoma, assessing pseudoprogression in melanoma, or predicting brain metastases in extracranial malignancies. Additionally, AI-assisted lesion segmentation, quantitative feature extraction, and heterogeneity analysis are contributing to improved prediction of treatment response and long-term survival outcomes. Despite encouraging results, variability in imaging protocols, segmentation methods, and validation strategies across studies continues to challenge reproducibility and remains a barrier to clinical translation. This review evaluates recent advancements of AI, its current clinical applications, and emphasizes the need for robust standardization and prospective validation to ensure the reproducibility and generalizability of AI tools in PET imaging and clinical practice.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 856-868"},"PeriodicalIF":5.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emil Novruzov, Eduards Mamlins, Yuriko Mori, Jens Cardinale, Frederik L. Giesel
{"title":"The Clinical Impact of FAPI PET Imaging: HCC, CCC, CUP & Peritoneal Carcinoma","authors":"Emil Novruzov, Eduards Mamlins, Yuriko Mori, Jens Cardinale, Frederik L. Giesel","doi":"10.1053/j.semnuclmed.2025.07.001","DOIUrl":"10.1053/j.semnuclmed.2025.07.001","url":null,"abstract":"<div><div>In recent years, FAP-targeted imaging has emerged as a highly-promising modality as a pan-cancer agent. Until now, several studies and review articles have focused on efficacy of FAPI imaging in epithelial malignancies with a high global incidence and prevalence such as lung cancer or GI-tumors. This work sought to shed light on diagnostic performance and clinical impact of FAPI imaging in rather low-incidence tumor-entities, which are nevertheless characterized by a poor outcome.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 724-733"},"PeriodicalIF":5.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radiotracing the Future: Non-FDG Radiotracers Nuclear Medicine","authors":"Giuseppe Arturo Fuso , Gianfilippo Bianciardi , Riccardo Mei , Irene Brusa , Stefano Emiliani , Emilia Fortunati , Cristina Nanni","doi":"10.1053/j.semnuclmed.2025.06.005","DOIUrl":"10.1053/j.semnuclmed.2025.06.005","url":null,"abstract":"<div><div>Positron Emission Tomography/Computed Tomography (PET/CT) is an advanced hybrid imaging modality that synergistically combines metabolic and anatomical data, revolutionizing diagnostic accuracy and therapeutic monitoring in various pathologies. While 18F-fluorodeoxyglucose (FDG) remains the cornerstone radiotracer for many oncologic and nononcologic applications, its limitations—such as nonspecific uptake in inflammation and limited sensitivity in certain tumor subtypes—have catalyzed the development and clinical adoption of non-FDG radiotracers. These novel agents exhibit diverse biological targets, enabling more precise characterization of tissue physiology and pathology. Among them, radiotracers such as 68Ga-DOTA Peptides, 18F-fluciclovine, 68Ga-PSMA, 11C-choline, and 18F-FDOPA have demonstrated utility in neuroendocrine tumors, prostate cancer, gliomas, and parkinsonian syndromes. Their application enhances disease detection, improves staging and restaging accuracy, and supports theranostic strategies. The integration of non-FDG PET tracers in clinical practice requires nuanced understanding of their pharmacokinetics, target specificity, and optimal imaging protocols. Furthermore, these tracers open avenues for personalized medicine, allowing for biomarker-guided management. As evidence continues to evolve, non-FDG PET/CT is poised to become indispensable in precision oncology and targeted molecular imaging across multiple disciplines.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 648-663"},"PeriodicalIF":5.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kim M. Pabst , Wolfgang P. Fendler , Leonie S. Jochheim , Ken Herrmann
{"title":"The Value of FAPI PET/CT in Cholangiocarcinoma and Pancreatic Cancer: An Update","authors":"Kim M. Pabst , Wolfgang P. Fendler , Leonie S. Jochheim , Ken Herrmann","doi":"10.1053/j.semnuclmed.2025.06.011","DOIUrl":"10.1053/j.semnuclmed.2025.06.011","url":null,"abstract":"<div><div>To date, contrast-enhanced CT (ceCT), magnetic resonance imaging (MRI), and, in selected cases, <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT) are the current standard imaging modalities for staging of pancreatic cancer and cholangiocarcinoma. Fibroblast activation protein alpha (FAP) has gained interest as a promising molecular imaging target, particularly in tumors with a pronounced desmoplastic reaction such as pancreatic cancer and cholangiocarcinoma. Radiolabeled FAP inhibitors (FAPIs) enable noninvasive visualization of cancer using PET/CT. Recent studies have demonstrated that FAPI PET/CT provides superior sensitivity compared to ceCT and <sup>18</sup>F-FDG PET/CT in cholangiocarcinoma and pancreatic cancer for detecting primary tumors, lymph node involvement, and distant metastases, particularly in hepatic metastases due to low physiological background uptake. Furthermore, FAPI PET/CT has been shown to affect TNM staging and subsequently alter treatment-decision making. Beyond staging, early evidence suggests a prognostic potential of FAPI PET/CT in tumor grading, therapy response assessment, and survival outcomes, although data remain limited. On the other hand, FAPI PET/CT comes with limitations, particularly in the context of fibrotic and inflammatory processes such as liver cirrhosis, pancreatitis, or primary sclerosing cholangitis, which may result in false-positive findings. This review summarizes the current clinical evidence for FAPI PET/CT in pancreatic cancer and cholangiocarcinoma, with a focus on diagnostic performance, prognostic relevance, therapeutic implications, and potential pitfalls.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 701-709"},"PeriodicalIF":5.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}