Pub Date : 2025-11-01Epub Date: 2025-09-26DOI: 10.1053/j.semnuclmed.2025.09.002
Zhi Chen , Zihan Li , Yu-Hua Huang , Tianyu Xiong , Xinzhi Teng , Bing Li , John Kipritidis , Paul J. Keall , Joseph M. Reinhardt , Hong Ge , Ge Ren , Jing Cai
Lung function imaging, with a specific focus on quantifying ventilation and perfusion, has gained increasing recognition within the field of functional lung avoidance radiation therapy (FLART), a technique that incorporates functional information to minimize radiation exposure to healthy lung tissue. This review critically analyzes multiple categories of clinical imaging modalities, including nuclear medicine imaging, computed tomography, and magnetic resonance imaging, which can assess the spatial distribution of lung functions. Each modality presents unique strengths in providing valuable information for FLART, yet they also have their limitations, which are detailed in this review. Furthermore, we discuss the current challenges limiting the broader implementation of lung function imaging and FLART in clinical practice. Future research directions and potential solutions are also outlined, to enable lung function imaging to play a more significant role in FLART, leading to personalized lung cancer management and improved patient outcomes.
{"title":"A Review of Advances in Lung Function Imaging and Its Applications for Functional Lung Avoidance in Radiation Therapy","authors":"Zhi Chen , Zihan Li , Yu-Hua Huang , Tianyu Xiong , Xinzhi Teng , Bing Li , John Kipritidis , Paul J. Keall , Joseph M. Reinhardt , Hong Ge , Ge Ren , Jing Cai","doi":"10.1053/j.semnuclmed.2025.09.002","DOIUrl":"10.1053/j.semnuclmed.2025.09.002","url":null,"abstract":"<div><div>Lung function imaging, with a specific focus on quantifying ventilation and perfusion, has gained increasing recognition within the field of functional lung avoidance radiation therapy (FLART), a technique that incorporates functional information to minimize radiation exposure to healthy lung tissue. This review critically analyzes multiple categories of clinical imaging modalities, including nuclear medicine imaging, computed tomography, and magnetic resonance imaging, which can assess the spatial distribution of lung functions. Each modality presents unique strengths in providing valuable information for FLART, yet they also have their limitations, which are detailed in this review. Furthermore, we discuss the current challenges limiting the broader implementation of lung function imaging and FLART in clinical practice. Future research directions and potential solutions are also outlined, to enable lung function imaging to play a more significant role in FLART, leading to personalized lung cancer management and improved patient outcomes.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 1046-1057"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177979","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: 2025-07-03DOI: 10.1053/j.semnuclmed.2025.06.007
Shaniqua A. Lawson, Jason S. Lewis
Ovarian cancer remains a leading cause of gynecologic cancer mortality, driven in part by late-stage diagnoses and high recurrence rates. Among emerging molecular targets, mucins—highly glycosylated transmembrane glycoproteins overexpressed and aberrantly glycosylated in epithelial ovarian cancers—have garnered increasing interest for both imaging and therapeutic strategies. This review highlights the expression profiles and clinical implications of key mucins (MUC1, MUC16) and evaluates antibody-based modalities that leverage these targets for enhanced tumor detection and treatment. We discuss the current landscape of therapeutic strategies, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and radioimmunotherapy, with emphasis on recent preclinical and clinical advances. We also examine the role of mucin-targeted antibodies in imaging and the integration of theranostic platforms. Key challenges such as antigen heterogeneity, immunogenicity, and tumor penetration are addressed, along with future directions for optimizing mucin-directed therapies. Together, these efforts underscore the ever-expanding potential of mucin-targeted immunotherapy to improve outcomes for patients with ovarian cancer.
{"title":"Mucin-Targeted Antibodies for Ovarian Cancer","authors":"Shaniqua A. Lawson, Jason S. Lewis","doi":"10.1053/j.semnuclmed.2025.06.007","DOIUrl":"10.1053/j.semnuclmed.2025.06.007","url":null,"abstract":"<div><div><span><span>Ovarian cancer remains a leading cause of </span>gynecologic cancer<span><span><span> mortality, driven in part by late-stage diagnoses and high recurrence rates. Among emerging molecular targets, mucins—highly glycosylated transmembrane glycoproteins overexpressed and aberrantly glycosylated in epithelial ovarian cancers—have garnered increasing interest for both imaging and therapeutic strategies. This review highlights the expression profiles and clinical implications of key mucins (MUC1, MUC16) and evaluates antibody-based modalities that leverage these targets for enhanced tumor detection and treatment. We discuss the current landscape of therapeutic strategies, including </span>monoclonal antibodies<span>, antibody-drug conjugates, bispecific antibodies<span>, and radioimmunotherapy, with emphasis on recent preclinical and clinical advances. We also examine the role of mucin-targeted antibodies in imaging and the integration of theranostic platforms. Key challenges such as antigen heterogeneity, </span></span></span>immunogenicity, and tumor penetration are addressed, along with future directions for optimizing mucin-directed therapies. Together, these efforts underscore the ever-expanding potential of mucin-targeted </span></span>immunotherapy to improve outcomes for patients with ovarian cancer.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 955-965"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565125","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: 2025-09-22DOI: 10.1053/j.semnuclmed.2025.08.003
Ayça Arçay Öztürk, Wendy Delbart, Patrick Flamen
Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment modality and is increasingly recognized as an immunomodulatory tool, similar to external beam radiotherapy (EBRT). Both forms of radiation can reshape the tumor immune microenvironment, providing a rationale for their combination with immune checkpoint inhibitors (ICIs) to harness synergistic effects while mitigating immunosuppressive mechanisms. Outcomes of such combinations depend on radiation dose/fractionation, treatment sequencing, target selection, and the choice of immunotherapeutic/radiopharmaceutical agents. Among novel TRT strategies, fibroblast activation protein-TRT (FAP-TRT) stands out for its targeting of cancer-associated fibroblasts (CAFs), key components of the tumor stroma involved in immune evasion and therapy resistance. Unlike conventional TRTs that directly target tumor cells, FAP-TRT acts on CAFs, potentially modulating the tumor microenvironment to enhance the immunomodulatory effects of radiation. This review examines the immunological effects of radiation—via EBRT or TRT-and the rationale for combining TRT with ICIs. We highlight preclinical and clinical studies demonstrating both the synergistic potential and context-specific limitations of TRT–ICI combinations. Emphasis is placed on the emerging role of FAP-TRT in remodeling the tumor microenvironment, converting “cold” tumors into “hot” phenotypes, and enhancing immune infiltration. Preclinical models show synergy between FAP-TRT and ICIs, but challenges remain, including clarifying FAP-TRT’s effects on CAF subpopulations, optimizing radiopharmaceutical design, and addressing shared issues with TRT/EBRT–ICI combinations, such as dosing, sequencing, and target selection. The integration of TRT and immunotherapy—particularly FAP-TRT combinations—offers a compelling avenue for precision oncology and warrants further translational and clinical investigation.
{"title":"Expanding the Horizon of Targeted Radionuclide Therapy: Immunotherapy Combinations and FAP-Targeted Approaches","authors":"Ayça Arçay Öztürk, Wendy Delbart, Patrick Flamen","doi":"10.1053/j.semnuclmed.2025.08.003","DOIUrl":"10.1053/j.semnuclmed.2025.08.003","url":null,"abstract":"<div><div>Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment modality and is increasingly recognized as an immunomodulatory tool, similar to external beam radiotherapy (EBRT). Both forms of radiation can reshape the tumor immune microenvironment, providing a rationale for their combination with immune checkpoint inhibitors (ICIs) to harness synergistic effects while mitigating immunosuppressive mechanisms. Outcomes of such combinations depend on radiation dose/fractionation, treatment sequencing, target selection, and the choice of immunotherapeutic/radiopharmaceutical agents. Among novel TRT strategies, fibroblast activation protein-TRT (FAP-TRT) stands out for its targeting of cancer-associated fibroblasts (CAFs), key components of the tumor stroma involved in immune evasion and therapy resistance. Unlike conventional TRTs that directly target tumor cells, FAP-TRT acts on CAFs, potentially modulating the tumor microenvironment to enhance the immunomodulatory effects of radiation. This review examines the immunological effects of radiation—via EBRT or TRT-and the rationale for combining TRT with ICIs. We highlight preclinical and clinical studies demonstrating both the synergistic potential and context-specific limitations of TRT–ICI combinations. Emphasis is placed on the emerging role of FAP-TRT in remodeling the tumor microenvironment, converting “cold” tumors into “hot” phenotypes, and enhancing immune infiltration. Preclinical models show synergy between FAP-TRT and ICIs, but challenges remain, including clarifying FAP-TRT’s effects on CAF subpopulations, optimizing radiopharmaceutical design, and addressing shared issues with TRT/EBRT–ICI combinations, such as dosing, sequencing, and target selection. The integration of TRT and immunotherapy—particularly FAP-TRT combinations—offers a compelling avenue for precision oncology and warrants further translational and clinical investigation.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 999-1010"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131881","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.2025.06.010
Akram Al-Ibraheem , Ahmed Saad Abdlkadir , Saad Ruzzeh , Marwah Abdulrahman , Serin Moghrabi , Rawa Ahmed , Hongcheng Shi , Fadi Khreish , Michael C. Kreissl , Rula Amarin , Kamal Al-Rabi , Asem Mansour , Hikmat Abdel-Razeq
[177Lu]Lu-FAPI, a novel and innovative radioligand targeting fibroblast activation protein (FAP), has rapidly emerged as a powerful therapeutic strategy for difficult-to-treat solid malignancies. FAP is highly expressed in cancer-associated fibroblasts (CAFs) across a broad spectrum of solid malignancies, thereby providing a valuable therapeutic target for novel radiopharmaceuticals. To date, a growing body of preliminary studies has explored the therapeutic potential of [177Lu]Lu-FAPI in oncology, with numerous ongoing clinical trials currently recruiting patients to substantiate its evolving prospects. This comprehensive review critically synthesizes current clinical evidence on [177Lu]Lu-FAPI radioligand therapy (RLT), outlining its available formulations, therapeutic efficacy, safety profile, recent advancements, challenges, and emerging applications across diverse tumor types. [177Lu]Lu-FAPI has shown considerable promise as an effective and relatively safe theranostic agent, with particular advantages in combination therapy approaches. Nevertheless, larger, well-controlled clinical studies are essential to establish its long-term efficacy and safety profile. Despite current limitations, this review underscores the emerging role of [177Lu]Lu-FAPI in oncological care, with growing relevance to personalized oncology strategies, and calls for further investigation to refine its clinical integration and maximize patient-specific outcomes.
{"title":"[177Lu]Lu-FAPI Radioligand Therapy: Emerging Horizons and Clinical Promise in Solid Tumors: A Comprehensive Review","authors":"Akram Al-Ibraheem , Ahmed Saad Abdlkadir , Saad Ruzzeh , Marwah Abdulrahman , Serin Moghrabi , Rawa Ahmed , Hongcheng Shi , Fadi Khreish , Michael C. Kreissl , Rula Amarin , Kamal Al-Rabi , Asem Mansour , Hikmat Abdel-Razeq","doi":"10.1053/j.semnuclmed.2025.06.010","DOIUrl":"10.1053/j.semnuclmed.2025.06.010","url":null,"abstract":"<div><div>[<sup>177</sup><span>Lu]Lu-FAPI, a novel and innovative radioligand<span><span> targeting fibroblast activation protein (FAP), has rapidly emerged as a powerful therapeutic strategy for difficult-to-treat solid malignancies. FAP is highly expressed in cancer-associated fibroblasts (CAFs) across a broad spectrum of solid malignancies, thereby providing a valuable therapeutic target for novel </span>radiopharmaceuticals. To date, a growing body of preliminary studies has explored the therapeutic potential of [</span></span><sup>177</sup><span>Lu]Lu-FAPI in oncology<span>, with numerous ongoing clinical trials currently recruiting patients to substantiate its evolving prospects. This comprehensive review critically synthesizes current clinical evidence on [</span></span><sup>177</sup><span>Lu]Lu-FAPI radioligand therapy (RLT), outlining its available formulations, therapeutic efficacy, safety profile, recent advancements, challenges, and emerging applications across diverse tumor types. [</span><sup>177</sup>Lu]Lu-FAPI has shown considerable promise as an effective and relatively safe theranostic agent, with particular advantages in combination therapy approaches. Nevertheless, larger, well-controlled clinical studies are essential to establish its long-term efficacy and safety profile. Despite current limitations, this review underscores the emerging role of [<sup>177</sup>Lu]Lu-FAPI in oncological care, with growing relevance to personalized oncology strategies, and calls for further investigation to refine its clinical integration and maximize patient-specific outcomes.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 988-998"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565123","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: 2025-09-12DOI: 10.1053/j.semnuclmed.2025.08.002
Ismaheel O. Lawal , Sofiullah Abubakar , Honest Ndlovu , Aisha Ismaila , Mike M. Sathekge
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.
{"title":"Radiolabeled Antibody–Drug Conjugates in the Treatment of Solid Tumors","authors":"Ismaheel O. Lawal , Sofiullah Abubakar , Honest Ndlovu , Aisha Ismaila , Mike M. Sathekge","doi":"10.1053/j.semnuclmed.2025.08.002","DOIUrl":"10.1053/j.semnuclmed.2025.08.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 889-902"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058617","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: 2025-10-08DOI: 10.1053/j.semnuclmed.2025.09.006
Keamogetswe Ramonaheng , Milani Qebetu , Kaluzi Banda , Pryaska Goorhoo , Khomotso Legodi , Sipho Mdanda , Sandile Sibiya , Yonwaba Mzizi , Honest Ndlovu , Joseph Kabunda , Mengdie Yang , Kuangyu Shi , Mike Sathekge
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.
{"title":"Advances in Dosimetry and Imaging for 203Pb and 212Pb Radiotheranostics","authors":"Keamogetswe Ramonaheng , Milani Qebetu , Kaluzi Banda , Pryaska Goorhoo , Khomotso Legodi , Sipho Mdanda , Sandile Sibiya , Yonwaba Mzizi , Honest Ndlovu , Joseph Kabunda , Mengdie Yang , Kuangyu Shi , Mike Sathekge","doi":"10.1053/j.semnuclmed.2025.09.006","DOIUrl":"10.1053/j.semnuclmed.2025.09.006","url":null,"abstract":"<div><div>Targeted alpha therapy (TAT) with <sup>212</sup>Pb 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, <sup>203</sup>Pb, 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 <sup>203</sup>Pb 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 <sup>203</sup>Pb/<sup>212</sup>Pb theranostic pair. The aim of this review is to provide a comprehensive assessment of <sup>212</sup>Pb-TAT, encompassing clinical applications, surrogate imaging with <sup>203</sup>Pb, gamma camera performance, dosimetry workflows, and predictive activity quantification, illustrating how these advances collectively enable quantitative, patient-specific, and theranostic-integrated radionuclide therapy.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 1011-1031"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252584","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":"Corrigendum to ‘18F-FDG PET for Dementia Evaluation: Co-pathologies, New Diseases, and Its Roles in The Era of Anti-Amyloid Treatment’ [Seminar in Nuclear Medicine volume 55 (2025):526 –537/Article number YSNUC_51208]","authors":"Tanyaluck Thientunyakit , Weerasak Muangpaisan , Satoshi Minoshima","doi":"10.1053/j.semnuclmed.2025.09.001","DOIUrl":"10.1053/j.semnuclmed.2025.09.001","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Page 1045"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178051","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: 2025-09-18DOI: 10.1053/j.semnuclmed.2025.08.001
Binyu Shi , Xinyuan Zhou , Junjun Zhou , Gang Huang , Jianjun Liu , Jin Zhang , Weijun Wei
The cluster of differentiation 70 (CD70), a transmembrane glycoprotein encoded by TNFSF7, is a member of the tumor necrosis factor (TNF) superfamily and serves as the ligand for the co-stimulatory receptor CD27. It is aberrantly overexpressed in various malignancies, including clear cell renal cell carcinoma (ccRCC) and nasopharyngeal carcinoma (NPC). Although CD70-directed radiotheranostics may address key challenges faced by antibody-drug conjugates (ADCs) and chimeric antigen receptor T (CAR-T) therapies, such as drug resistance and tumor penetration barriers, this therapeutic approach remains unexplored in clinical settings. In this review, we highlight the expression of CD70 in normal tissues and organs, as well as in different tumor types, presenting promising results from CD70-targeted immuno-PET/CT imaging in recent clinical trials. Furthermore, we emphasize relevant therapeutic radiopharmaceuticals currently in preclinical or clinical trials, providing a rational roadmap for guiding future development of CD70-targeted radiotheranostics.
{"title":"CD70-Targeted Radiotheranostics: Now and Future","authors":"Binyu Shi , Xinyuan Zhou , Junjun Zhou , Gang Huang , Jianjun Liu , Jin Zhang , Weijun Wei","doi":"10.1053/j.semnuclmed.2025.08.001","DOIUrl":"10.1053/j.semnuclmed.2025.08.001","url":null,"abstract":"<div><div>The cluster of differentiation 70 (CD70), a transmembrane glycoprotein encoded by <em>TNFSF7</em>, is a member of the tumor necrosis factor (TNF) superfamily and serves as the ligand for the co-stimulatory receptor CD27. It is aberrantly overexpressed in various malignancies, including clear cell renal cell carcinoma (ccRCC) and nasopharyngeal carcinoma (NPC). Although CD70-directed radiotheranostics may address key challenges faced by antibody-drug conjugates (ADCs) and chimeric antigen receptor T (CAR-T) therapies, such as drug resistance and tumor penetration barriers, this therapeutic approach remains unexplored in clinical settings. In this review, we highlight the expression of CD70 in normal tissues and organs, as well as in different tumor types, presenting promising results from CD70-targeted immuno-PET/CT imaging in recent clinical trials. Furthermore, we emphasize relevant therapeutic radiopharmaceuticals currently in preclinical or clinical trials, providing a rational roadmap for guiding future development of CD70-targeted radiotheranostics.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 903-911"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091979","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}
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.
{"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":"10.1053/j.semnuclmed.2025.07.003","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 6","pages":"Pages 937-946"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","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}
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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号