Astatine (211At) is an alpha-emitting nuclide with a 7.2-hour half-life that can be produced using a 30-MeV cyclotron. In recent years, the number of production sites worldwide has been increasing, attracting growing attention to 211At. We have developed a novel 211At-labeled PSMA-targeted agent ([211At]PSMA-5). After conducting preclinical evaluations of its antitumor efficacy and safety, we initiated a first-in-human, investigator-initiated clinical trial in patients with metastatic castration-resistant prostate cancer. To date, the drug has been administered to a total of nine patients, and we have reported high accumulation of [211At]PSMA-5 in recurrent and metastatic lesions. While further efforts are required for the social implementation of 211At-based targeted alpha therapy, including the establishment of a supply chain and the accumulation of additional clinical evidence, PSMA-targeted alpha therapy using 211At represents a promising treatment modality owing to its cyclotron-based production, sustainability, and clean decay characteristics.
{"title":"Development of PSMA-Targeted Alpha Therapy Using [211At]PSMA-5","authors":"Tadashi Watabe , Sadahiro Naka , Yoshifumi Shirakami , Kazuko Kaneda , Masashi Murakami , Atsushi Toyoshima , Jens Cardinale , Frederik L. Giesel","doi":"10.1053/j.semnuclmed.2025.09.005","DOIUrl":"10.1053/j.semnuclmed.2025.09.005","url":null,"abstract":"<div><div>Astatine (<sup>211</sup>At) is an alpha-emitting nuclide with a 7.2-hour half-life that can be produced using a 30-MeV cyclotron. In recent years, the number of production sites worldwide has been increasing, attracting growing attention to <sup>211</sup>At. We have developed a novel <sup>211</sup>At-labeled PSMA-targeted agent ([<sup>211</sup>At]PSMA-5). After conducting preclinical evaluations of its antitumor efficacy and safety, we initiated a first-in-human, investigator-initiated clinical trial in patients with metastatic castration-resistant prostate cancer. To date, the drug has been administered to a total of nine patients, and we have reported high accumulation of [<sup>211</sup>At]PSMA-5 in recurrent and metastatic lesions. While further efforts are required for the social implementation of <sup>211</sup>At-based targeted alpha therapy, including the establishment of a supply chain and the accumulation of additional clinical evidence, PSMA-targeted alpha therapy using <sup>211</sup>At represents a promising treatment modality owing to its cyclotron-based production, sustainability, and clean decay characteristics.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 947-954"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207337","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}
Pub Date : 2025-11-01Epub Date: 2025-09-27DOI: 10.1053/j.semnuclmed.2025.09.003
Joseph Kabunda , Honest Ndlovu , Karishma Singh , Sandile Sibiya , Sipho Mdanda , Kamo Ramonaheng , Akram Al-Ibraheem , Ken Herrmann , Kgomotso Mokoala , Mike Sathekge
Bladder cancer is among the top ten most common cancers globally, with advanced or metastatic disease associated with dismal survival outcomes. Current diagnostic imaging and therapies have significant limitations, highlighting the urgent need for novel theranostic targets. Nectin-4, a cell adhesion molecule frequently overexpressed in bladder cancer, especially urothelial carcinoma (∼60%-87% of tumors), has emerged as a promising biomarker and therapeutic target. This review critically evaluates the role of Nectin-4 in bladder cancer and explores its exciting potential in nuclear medicine for combined molecular imaging and targeted radionuclide therapy—embracing the "theranostic" paradigm. Nectin-4 is abundantly and selectively expressed in most urothelial carcinomas, correlating with advanced disease and poorer prognosis. Clinically validated by the FDA-approved antibody-drug conjugate enfortumab vedotin, Nectin-4 targeting achieves objective response rates around 40%-50% and significantly improves survival in refractory advanced urothelial carcinoma. Recent clinical advances in Nectin-4–targeted PET imaging (such as 68Ga-labeled agents) have demonstrated excellent tumor localization and specificity, enabling precise patient selection for targeted therapies. Additionally, emerging radionuclide therapeutics (eg, 225Ac- and 177Lu-based agents) show promising preclinical and early clinical efficacy, robust tumor targeting, and favorable safety profiles. Targeting Nectin-4 represents a new frontier in the management of bladder cancer, bridging the gap between precise molecular diagnostics and personalized targeted radionuclide therapy. Ongoing clinical trials and translational research are rapidly advancing this promising theranostic strategy towards routine clinical application, with significant potential to enhance patient selection, treatment monitoring, and ultimately, clinical outcomes.
{"title":"Nectin-4, Bladder Cancer, and Nuclear Medicine: A Theranostic Frontier","authors":"Joseph Kabunda , Honest Ndlovu , Karishma Singh , Sandile Sibiya , Sipho Mdanda , Kamo Ramonaheng , Akram Al-Ibraheem , Ken Herrmann , Kgomotso Mokoala , Mike Sathekge","doi":"10.1053/j.semnuclmed.2025.09.003","DOIUrl":"10.1053/j.semnuclmed.2025.09.003","url":null,"abstract":"<div><div>Bladder cancer is among the top ten most common cancers globally, with advanced or metastatic disease associated with dismal survival outcomes. Current diagnostic imaging and therapies have significant limitations, highlighting the urgent need for novel theranostic targets. Nectin-4, a cell adhesion molecule frequently overexpressed in bladder cancer, especially urothelial carcinoma (∼60%-87% of tumors), has emerged as a promising biomarker and therapeutic target. This review critically evaluates the role of Nectin-4 in bladder cancer and explores its exciting potential in nuclear medicine for combined molecular imaging and targeted radionuclide therapy—embracing the \"theranostic\" paradigm. Nectin-4 is abundantly and selectively expressed in most urothelial carcinomas, correlating with advanced disease and poorer prognosis. Clinically validated by the FDA-approved antibody-drug conjugate enfortumab vedotin, Nectin-4 targeting achieves objective response rates around 40%-50% and significantly improves survival in refractory advanced urothelial carcinoma. Recent clinical advances in Nectin-4–targeted PET imaging (such as <sup>68</sup>Ga-labeled agents) have demonstrated excellent tumor localization and specificity, enabling precise patient selection for targeted therapies. Additionally, emerging radionuclide therapeutics (eg, <sup>225</sup>Ac- and <sup>177</sup>Lu-based agents) show promising preclinical and early clinical efficacy, robust tumor targeting, and favorable safety profiles. Targeting Nectin-4 represents a new frontier in the management of bladder cancer, bridging the gap between precise molecular diagnostics and personalized targeted radionuclide therapy. Ongoing clinical trials and translational research are rapidly advancing this promising theranostic strategy towards routine clinical application, with significant potential to enhance patient selection, treatment monitoring, and ultimately, clinical outcomes.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 912-927"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182222","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}
Pub Date : 2025-11-01Epub Date: 2025-08-11DOI: 10.1053/j.semnuclmed.2025.07.002
Kalyan Mansukhbhai Shekhda , Shaunak Navalkissoor
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.
{"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":"10.1053/j.semnuclmed.2025.07.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 966-974"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-08-31DOI: 10.1053/j.semnuclmed.2025.07.005
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
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.
{"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":"10.1053/j.semnuclmed.2025.07.005","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 1032-1044"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-07-04DOI: 10.1053/j.semnuclmed.2025.06.008
Kunal Ramesh Chandekar, Chandrasekhar Bal
225Ac-DOTATATE-based targeted alpha therapy (TAT) is emerging as a transformative option in the management of advanced, well-differentiated, somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs), particularly in patients refractory to conventional β-emitter peptide receptor radionuclide therapy (PRRT). This review synthesizes current evidence from preclinical models and early-phase clinical studies, highlighting its therapeutic promise in terms of potent antitumor efficacy and favorable toxicity profile. We discuss the radiobiological and mechanistic advantages of α-particle therapy while also addressing key limitations such as radionuclide supply constraints, recoil-induced daughter redistribution, challenges in dosimetry, and regulatory hurdles. Emerging strategies including improved chelators, SSTR antagonists, and tandem or combination therapies are described. Key ongoing trials have also been summarized. As 225Ac-DOTATATE-based TAT progresses toward mainstream clinical integration, multidisciplinary collaboration across academia, industry, and regulatory bodies will be essential to refine protocols, optimize safety, and expand access.
{"title":"Advances With 225Ac-DOTATATE Targeted Alpha Therapy in Somatostatin Receptor Positive Neuroendocrine Tumors","authors":"Kunal Ramesh Chandekar, Chandrasekhar Bal","doi":"10.1053/j.semnuclmed.2025.06.008","DOIUrl":"10.1053/j.semnuclmed.2025.06.008","url":null,"abstract":"<div><div><sup>225</sup><span><span>Ac-DOTATATE-based targeted alpha therapy (TAT) is emerging as a transformative option in the management of advanced, well-differentiated, somatostatin receptor<span> (SSTR)-positive neuroendocrine tumors<span> (NETs), particularly in patients refractory to conventional β-emitter peptide receptor </span></span></span>radionuclide<span><span> therapy (PRRT). This review synthesizes current evidence from preclinical models and early-phase clinical studies, highlighting its therapeutic promise in terms of potent antitumor efficacy and favorable toxicity profile. We discuss the radiobiological and mechanistic advantages of α-particle therapy while also addressing key limitations such as radionuclide supply constraints, recoil-induced daughter redistribution, challenges in </span>dosimetry<span>, and regulatory hurdles. Emerging strategies including improved chelators<span>, SSTR antagonists, and tandem or combination therapies are described. Key ongoing trials have also been summarized. As </span></span></span></span><sup>225</sup>Ac-DOTATATE-based TAT progresses toward mainstream clinical integration, multidisciplinary collaboration across academia, industry, and regulatory bodies will be essential to refine protocols, optimize safety, and expand access.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 975-987"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565124","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}
Pub Date : 2025-11-01Epub Date: 2025-09-27DOI: 10.1053/j.semnuclmed.2025.09.004
Luca Filippi
Glypican-3 (GPC3) is a membrane-anchored heparan sulfate proteoglycan overexpressed in many hepatocellular carcinomas (HCCs) while minimally present in normal adult liver, making it an attractive target for integrated diagnostic and therapeutic ("theranostic") strategies. This review synthesizes preclinical and early clinical efforts to exploit GPC3 for targeted PET imaging and radionuclide therapy. Imaging approaches have evolved from 89Zr- and 124I-labeled full antibodies—demonstrating robust, delayed tumor localization—to smaller scaffolds (F(ab')₂, single-domain antibodies, peptides) paired with 18F or 68Ga for same-day, high-contrast imaging. First-in-human studies, including 124I-codrituzumab and 68Ga-RAYZ-8009, confirmed tumor-specific accumulation but remained limited in scale. Therapeutic investigations spanned beta-emitters (90Y, 177Lu) and high-LET alpha-emitters (225Ac, 227Th), showing potent antitumor effects in orthotopic and xenograft models yet raising dosimetric and toxicity concerns—especially for long-circulating antibody carriers and alpha therapies. Key translational challenges include hepatic background clearance, intra-patient heterogeneity of GPC3 expression, rigorous dosimetry, toxicology in larger species, and radionuclide supply logistics. The available evidence suggests a preferential pathway, involving the selection of a limited set of lead vectors, their pairing with suitable radionuclides, validation in orthotopic/PDX models using standardized endpoints, and the integration of comprehensive dosimetric and toxicologic studies before proceeding to broader human trials. GPC3-directed theranostics thus offers a compelling, disease-specific route to precision management of HCC, provided translational rigor addresses the outlined safety and quantitative imaging gaps.
{"title":"Glypican-3: Novel Theranostic Agent for Hepatocellular Carcinoma","authors":"Luca Filippi","doi":"10.1053/j.semnuclmed.2025.09.004","DOIUrl":"10.1053/j.semnuclmed.2025.09.004","url":null,"abstract":"<div><div>Glypican-3 (GPC3) is a membrane-anchored heparan sulfate proteoglycan overexpressed in many hepatocellular carcinomas (HCCs) while minimally present in normal adult liver, making it an attractive target for integrated diagnostic and therapeutic (\"theranostic\") strategies. This review synthesizes preclinical and early clinical efforts to exploit GPC3 for targeted PET imaging and radionuclide therapy. Imaging approaches have evolved from <sup>89</sup>Zr- and <sup>124</sup>I-labeled full antibodies—demonstrating robust, delayed tumor localization—to smaller scaffolds (F(ab')₂, single-domain antibodies, peptides) paired with <sup>18</sup>F or <sup>68</sup>Ga for same-day, high-contrast imaging. First-in-human studies, including <sup>124</sup>I-codrituzumab and <sup>68</sup>Ga-RAYZ-8009, confirmed tumor-specific accumulation but remained limited in scale. Therapeutic investigations spanned beta-emitters (<sup>90</sup>Y, <sup>177</sup>Lu) and high-LET alpha-emitters (<sup>225</sup>Ac, <sup>227</sup>Th), showing potent antitumor effects in orthotopic and xenograft models yet raising dosimetric and toxicity concerns—especially for long-circulating antibody carriers and alpha therapies. Key translational challenges include hepatic background clearance, intra-patient heterogeneity of GPC3 expression, rigorous dosimetry, toxicology in larger species, and radionuclide supply logistics. The available evidence suggests a preferential pathway, involving the selection of a limited set of lead vectors, their pairing with suitable radionuclides, validation in orthotopic/PDX models using standardized endpoints, and the integration of comprehensive dosimetric and toxicologic studies before proceeding to broader human trials. GPC3-directed theranostics thus offers a compelling, disease-specific route to precision management of HCC, provided translational rigor addresses the outlined safety and quantitative imaging gaps.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 928-936"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182235","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}
Pub Date : 2025-11-01Epub Date: 2025-10-24DOI: 10.1053/j.semnuclmed.2025.09.007
M Michael Sathekge, Kirsten Bouchelouche
{"title":"Letter from the Editors","authors":"M Michael Sathekge, Kirsten Bouchelouche","doi":"10.1053/j.semnuclmed.2025.09.007","DOIUrl":"10.1053/j.semnuclmed.2025.09.007","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 885-888"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366139","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}
Pub Date : 2025-09-01Epub Date: 2025-05-06DOI: 10.1053/j.semnuclmed.2025.04.004
Anita Brink , Diana Paez , Enrique Estrada Lobato , Roberto C. Delgado Bolton , Peter Knoll , Aruna Korde , Adriana K. Calapaquí Terán , Mohamad Haidar , Francesco Giammarile
Nuclear medicine is rapidly evolving with new molecular imaging targets and advanced computational tools that promise to enhance diagnostic precision and personalized therapy. Recent years have seen a surge in novel PET and SPECT tracers, such as those targeting prostate-specific membrane antigen (PSMA) in prostate cancer, fibroblast activation protein (FAP) in tumor stroma, and tau protein in neurodegenerative disease. These tracers enable more specific visualization of disease processes compared to traditional agents, fitting into a broader shift toward precision imaging in oncology and neurology. In parallel, artificial intelligence (AI) and machine learning techniques are being integrated into tracer development and image analysis. AI-driven methods can accelerate radiopharmaceutical discovery, optimize pharmacokinetic properties, and assist in interpreting complex imaging datasets. This editorial provides an expanded overview of emerging imaging targets and techniques, including theranostic applications that pair diagnosis with radionuclide therapy, and examines how AI is augmenting nuclear medicine. We discuss the implications of these advancements within the field’s historical trajectory and address the regulatory, manufacturing, and clinical challenges that must be navigated. Innovations in molecular targeting and AI are poised to transform nuclear medicine practice, enabling more personalized diagnostics and radiotheranostic strategies in the era of precision healthcare.
{"title":"New Targets for Imaging in Nuclear Medicine","authors":"Anita Brink , Diana Paez , Enrique Estrada Lobato , Roberto C. Delgado Bolton , Peter Knoll , Aruna Korde , Adriana K. Calapaquí Terán , Mohamad Haidar , Francesco Giammarile","doi":"10.1053/j.semnuclmed.2025.04.004","DOIUrl":"10.1053/j.semnuclmed.2025.04.004","url":null,"abstract":"<div><div>Nuclear medicine is rapidly evolving with new molecular imaging targets and advanced computational tools that promise to enhance diagnostic precision and personalized therapy. Recent years have seen a surge in novel PET and SPECT tracers, such as those targeting prostate-specific membrane antigen (PSMA) in prostate cancer, fibroblast activation protein (FAP) in tumor stroma, and tau protein in neurodegenerative disease. These tracers enable more specific visualization of disease processes compared to traditional agents, fitting into a broader shift toward precision imaging in oncology and neurology. In parallel, artificial intelligence (AI) and machine learning techniques are being integrated into tracer development and image analysis. AI-driven methods can accelerate radiopharmaceutical discovery, optimize pharmacokinetic properties, and assist in interpreting complex imaging datasets. This editorial provides an expanded overview of emerging imaging targets and techniques, including theranostic applications that pair diagnosis with radionuclide therapy, and examines how AI is augmenting nuclear medicine. We discuss the implications of these advancements within the field’s historical trajectory and address the regulatory, manufacturing, and clinical challenges that must be navigated. Innovations in molecular targeting and AI are poised to transform nuclear medicine practice, enabling more personalized diagnostics and radiotheranostic strategies in the era of precision healthcare.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 869-884"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013197","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}
Pub Date : 2025-09-01Epub Date: 2025-05-29DOI: 10.1053/j.semnuclmed.2025.05.001
Esther Mena , Liza Lindenberg , Peter Herscovitch , Samira M. Sadowski , Peter L. Choyke
Molecular imaging has experienced significant advances in the areas of imaging probes and technology, enabling the detection of tumors at earlier stages and more accurately identifying extent of disease. To better characterize lesions, nuclear medicine modalities utilize molecular imaging agents targeting specific pathways and cell surface molecules to improve both sensitivity and specificity. In the field of endocrinology, tumors encompass a wide spectrum of aggressiveness ranging from indolent, well differentiated tumors to highly aggressive cancers. Thus, in recent years, new molecular imaging biomarkers have been developed for noninvasively assessing different types of hormone-producing tumors. For instance, 68Ga-PentixaFor is a novel PET imaging agent targeting the C-X-C chemokine receptor type 4 (CXCR4) with proven utility in various malignancies, and has also shown multifunctionality in detecting endocrine pathologies, such as primary aldosteronism, adrenocorticotropic hormone (ACTH)-producing pituitary adenomas and ACTH-independent cortisol-producing adrenal adenomas. Another novel receptor-targeted radiotracer using the glucagon-like peptide-1 receptor (GLP-1R) analog, Exendin-4 has recently developed to preoperatively localize insulinomas, arising from pancreatic beta cells. This review presents an overview of new developments and potential clinical implementation of CXCR4- and Exendin- based radiotracers for imaging applications in endocrinology.
{"title":"Advances in Endocrine Tumor PET Imaging Targeting CXCR4 and GLP-1","authors":"Esther Mena , Liza Lindenberg , Peter Herscovitch , Samira M. Sadowski , Peter L. Choyke","doi":"10.1053/j.semnuclmed.2025.05.001","DOIUrl":"10.1053/j.semnuclmed.2025.05.001","url":null,"abstract":"<div><div>Molecular imaging has experienced significant advances in the areas of imaging probes and technology, enabling the detection of tumors at earlier stages and more accurately identifying extent of disease. To better characterize lesions, nuclear medicine modalities utilize molecular imaging agents targeting specific pathways and cell surface molecules to improve both sensitivity and specificity. In the field of endocrinology, tumors encompass a wide spectrum of aggressiveness ranging from indolent, well differentiated tumors to highly aggressive cancers. Thus, in recent years, new molecular imaging biomarkers have been developed for noninvasively assessing different types of hormone-producing tumors. For instance, <sup>68</sup>Ga-PentixaFor is a novel PET imaging agent targeting the C-X-C chemokine receptor type 4 (CXCR4) with proven utility in various malignancies, and has also shown multifunctionality in detecting endocrine pathologies, such as primary aldosteronism, adrenocorticotropic hormone (ACTH)-producing pituitary adenomas and ACTH-independent cortisol-producing adrenal adenomas. Another novel receptor-targeted radiotracer using the glucagon-like peptide-1 receptor (GLP-1R) analog, Exendin-4 has recently developed to preoperatively localize insulinomas, arising from pancreatic beta cells. This review presents an overview of new developments and potential clinical implementation of CXCR4- and Exendin- based radiotracers for imaging applications in endocrinology.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 766-775"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187871","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}
Pub Date : 2025-09-01Epub Date: 2025-06-01DOI: 10.1053/j.semnuclmed.2025.05.003
Roberto C. Delgado Bolton , Adriana K. Calapaquí Terán , Ludmila Santiago Almeida , Diana Paez , Enrique Estrada Lobato , Anita Brink , Peter Knoll , Giorgio Treglia , Francesco Giammarile
Nuclear medicine has seen significant advancements in recent years, especially in the area of Positron Emission Tomography (PET) imaging. One of these innovations is the use of Fibroblast Activation Protein Inhibitors (FAPI) as a novel radiotracer. FAPI PET imaging has shown promising results in various malignancies, including sarcomas, which are a diverse group of cancers originating from mesenchymal cells. This review aims to explore the potential of FAPI PET imaging in the diagnosis, staging, and treatment monitoring of sarcomas. Several studies have demonstrated the potential of FAPI PET in sarcomas. Furthermore, FAPI PET imaging has shown potential in assessing treatment response, with changes in FAPI uptake correlating with treatment outcomes. However, there are challenges to be addressed. The heterogeneity of sarcomas, both inter- and intra-tumoral, may affect the uniformity of Fibroblast Activation Protein (FAP) expression and thus the effectiveness of FAPI PET imaging. In conclusion, the introduction of FAPI PET imaging represents a significant advancement in the field of nuclear medicine and oncology. As we continue to deepen our understanding of this novel imaging technique, it is hoped that FAPI PET imaging will play an increasingly important role in the fight against cancer. However, as with any new technology, further research is needed to fully understand the potential and limitations of FAPI PET imaging in the clinical setting.
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