Tadashi Watabe, Sadahiro Naka, Yoshifumi Shirakami, Kazuko Kaneda, Masashi Murakami, Atsushi Toyoshima, Jens Cardinale, Frederik L Giesel
{"title":"Development of PSMA-Targeted Alpha Therapy Using [<sup>211</sup>At]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":"https://doi.org/10.1053/j.semnuclmed.2025.09.005","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-30","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}
Joseph Kabunda, Honest Ndlovu, Karishma Singh, Sandile Sibiya, Sipho Mdanda, Kamo Ramonaheng, Akram Al-Ibraheem, Ken Herrmann, Kgomotso Mokoala, Mike Sathekge
{"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":"https://doi.org/10.1053/j.semnuclmed.2025.09.003","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-26","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}
{"title":"Glypican-3: Novel Theranostic Agent for Hepatocellular Carcinoma.","authors":"Luca Filippi","doi":"10.1053/j.semnuclmed.2025.09.004","DOIUrl":"https://doi.org/10.1053/j.semnuclmed.2025.09.004","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-26","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}
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
{"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":"https://doi.org/10.1053/j.semnuclmed.2025.09.002","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-25","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}
{"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":"https://doi.org/10.1053/j.semnuclmed.2025.09.001","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-25","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}
{"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":"https://doi.org/10.1053/j.semnuclmed.2025.08.003","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-22","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}
Binyu Shi, Xinyuan Zhou, Junjun Zhou, Gang Huang, Jianjun Liu, Jin Zhang, Weijun Wei
{"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":"https://doi.org/10.1053/j.semnuclmed.2025.08.001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-18","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}
Ismaheel O Lawal, Sofiullah Abubakar, Honest Ndlovu, Aisha Ismaila, Mike M Sathekge
{"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":"https://doi.org/10.1053/j.semnuclmed.2025.08.002","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","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}
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}