{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T19:09:28Z","timestamp":1757617768974,"version":"3.44.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K16489"],"award-info":[{"award-number":["17K16489"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005119","name":"Japan Atomic Energy Research Institute","doi-asserted-by":"publisher","award":["H30-2"],"award-info":[{"award-number":["H30-2"]}],"id":[{"id":"10.13039\/501100005119","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018790","name":"National Institutes for Quantum and Radiological Science and Technology","doi-asserted-by":"publisher","award":["2022A-C01","2023A-C01"],"award-info":[{"award-number":["2022A-C01","2023A-C01"]}],"id":[{"id":"10.13039\/501100018790","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Jpn J Radiol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>A theranostic nanomedicine for CD3<jats:sup>+<\/jats:sup> bispecific antibodies targeting glycoprotein-100 (GP-100) was tested in vivo using two radiation sessions. CT-imageable nanoparticles composed of hyaluronate-alginate and designed to release their contents upon radiation exposure were evaluated in a mouse model of B16-melanoma model in the left hind leg with pulmonary metastases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Materials and Methods<\/jats:title>\n            <jats:p>In session 1, IFN-\u03b3 was encapsulated during the Fe polymerization of hyaluronate-alginate nanoparticles. Nine hours after the intravenous injection of 1\u2009\u00d7\u200910<jats:sup>10<\/jats:sup> IFN-\u03b3 nanoparticles, enough to observe dose escalation of either 10 or 20\u00a0Gy was administered using 140\u00a0keV-X-ray to the primary and metastatic tumors. In session 2, tebentafusp was encapsulated using the same method as in session 1. Seventy-two hours after the intravenous injection of 1\u2009\u00d7\u200910<jats:sup>10<\/jats:sup> tebentafusp-loaded nanoparticles, radiation was administered under conditions identical to those in session 1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In session 1, IFN-\u03b3-loaded nanoparticles selectively accumulated in the primary tumor and pulmonary metastasis by passing through the coarse endothelium of tumor vasculature, which could be visualized using CT. IFN-\u03b3 nanoparticles continuously released IFN-\u03b3, facilitating the formation of the HLA-A*02:01-GP100-complex. In session 2, the tebentafusp-loaded nanoparticles continuously released tebentafusp, leading to the formation of an immunological synapse consisting of HLA-A*02:01-GP100, tebentafusp, and CD3 on T cells. CD3<jats:sup>+<\/jats:sup> T cells release perforin and granzymes, resulting in the cytolysis of the primary tumor and pulmonary metastasis. This effect was synergistic with that of radiation, resulting in Enhancement Factor (EF) more than 1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Theranostic nanomedicine demonstrated potential as a dual therapeutic and diagnostic strategy for targeting tumors and metastases, with synergistic effects observed when combined with radiation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s11604-025-01782-w","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T01:32:50Z","timestamp":1744853570000},"page":"1393-1407","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted theranostic nanomedicine using targeted CT-imageable particles that release tebentafusp."],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2208-9689","authenticated-orcid":false,"given":"Satoshi","family":"Harada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Yoshioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"1782_CR1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/s41392-023-01462-z","volume":"8","author":"S Guo","year":"2023","unstructured":"Guo S, Yao Y, Tang Y, Xin Z, Dang Wu, Ni C, et al. Radiation-induced tumor immune microenvironments and potential targets for combination therapy. Signal Transduct Target Ther. 2023;8:205\u201326. https:\/\/doi.org\/10.1038\/s41392-023-01462-z.","journal-title":"Signal Transduct Target Ther"},{"key":"1782_CR2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j-cellimm.2016.04.005","volume":"303","author":"CE Gallegos","year":"2016","unstructured":"Gallegos CE, Michelin S, Duvner D, Arosella ED. Immunomodulation of classical and non-classical HLA modulation by ionizing radiation. Cell Immunol. 2016;303:16\u201323. https:\/\/doi.org\/10.1016\/j-cellimm.2016.04.005.","journal-title":"Cell Immunol"},{"key":"1782_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.04.030","author":"Y Uchihara","year":"2022","unstructured":"Uchihara Y, Bunga T, Permata M, Sato H, Kawabata-Iwakawa R, Katada S, Wenchao Gu, et al. DNA damage promotes HLA classI presentation by stimulating a pioneer round of translation-associated antigen production. Mol Cell. 2022. https:\/\/doi.org\/10.1016\/j.molcel.2022.04.030.","journal-title":"Mol Cell"},{"key":"1782_CR4","doi-asserted-by":"publisher","first-page":"5968","DOI":"10.3390\/cancers13235968","volume":"13","author":"D Martinez-Perez","year":"2021","unstructured":"Martinez-Perez D, Vinal D, Solares I, Espinosa E, Feliu J. GP-100 as a Novel therapeutic target in uveal melanoma. Cancer. 2021;13:5968\u201377. https:\/\/doi.org\/10.3390\/cancers13235968.","journal-title":"Cancer"},{"key":"1782_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40364-020-00228-x","volume":"8","author":"D Jorgovanovic","year":"2020","unstructured":"Jorgovanovic D, Song M, Wang L, Zhang Yi. Roles of IFN-\u03b3 in tumor progression and regression. Biomarker Research. 2020;8:1\u201316. https:\/\/doi.org\/10.1186\/s40364-020-00228-x.","journal-title":"Biomarker Research"},{"issue":"24","key":"1782_CR6","doi-asserted-by":"publisher","first-page":"6447","DOI":"10.1158\/1078-0432.CCR-18-1139","volume":"24","author":"Ji Li","year":"2018","unstructured":"Li Ji, Ybarra R, Mak J, Herault A, De Almeida P, Arrazate A, Ziai J, Totpal K, Junttila MR, Walsh KB. IFN\u03b3-induced chemokines are required for CXCR3-mediated T-cell recruitment and antitumor efficacy of anti-HER2\/CD3Bispecific antibody. Clin Cancer Res. 2018;24(24):6447\u201358. https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-1139.","journal-title":"Clin Cancer Res"},{"key":"1782_CR7","doi-asserted-by":"publisher","first-page":"5869","DOI":"10.1158\/1078-0432.CCR-20-1247","volume":"26","author":"MR Middleton","year":"2020","unstructured":"Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR, Steven NM, et al. Tabentafusp, A TCR\/Anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res. 2020;26:5869\u201378. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-1247.","journal-title":"Clin Cancer Res"},{"key":"1782_CR8","doi-asserted-by":"publisher","first-page":"112986","DOI":"10.1016\/j.ejca.2023.112986","volume":"191","author":"JC Hassel","year":"2023","unstructured":"Hassel JC, Berking C, Forschner A, Gebhardt C, Heinzerling L, Meier F, et al. Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp. Eur J Cancer. 2023;191:112986\u201398. https:\/\/doi.org\/10.1016\/j.ejca.2023.112986.","journal-title":"Eur J Cancer"},{"issue":"2","key":"1782_CR9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.ijrobp.2009.02.082","volume":"75","author":"S Harada","year":"2009","unstructured":"Harada S, Ehara S, Ishii K, Hiromichi Yamazaki Y, Shigeo Matsuyama Y, Sato T, et al. Targeted delivery of chemotherapeutic agents using improved radiosensitive liquid core microcapsules and assessment of their antitumor effect. Int J Radiation Oncol, Biol, Phys. 2009;75(2):455\u201362. https:\/\/doi.org\/10.1016\/j.ijrobp.2009.02.082.","journal-title":"Int J Radiation Oncol, Biol, Phys"},{"key":"1782_CR10","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.biopha.2015.01.006","volume":"70","author":"S Harada","year":"2015","unstructured":"Harada S, Ehara S, Ishii K, Sato T, Koka M, Kamiya T, et al. Targeted concurrent chemoradiotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo. Biomed Pharmacother. 2015;70:196\u2013205. https:\/\/doi.org\/10.1016\/j.biopha.2015.01.006.","journal-title":"Biomed Pharmacother"},{"key":"1782_CR11","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1667\/RR15357.1","volume":"193","author":"T Segawa","year":"2020","unstructured":"Segawa T, Harada S, Sato T, Ehara S. Delivery and effectiveness of carboplatin via targeted delivery compared to passive accumulation of intravenously injected particles releasing carboplatin upon irradiation. Radiation Res. 2020;193:263\u201373. https:\/\/doi.org\/10.1667\/RR15357.1.","journal-title":"Radiation Res"},{"key":"1782_CR12","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.addr.2013.11.009","volume":"66","author":"N Bertrand","year":"2014","unstructured":"Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2\u201325. https:\/\/doi.org\/10.1016\/j.addr.2013.11.009.","journal-title":"Adv Drug Deliv Rev"},{"key":"1782_CR13","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1142\/S0129083502000160","volume":"8","author":"S Matsuyama","year":"1998","unstructured":"Matsuyama S, Ishii K, Sugimoto A, Satoh T, Gotoh K, Yamazaki H, et al. Development of Micro-PIXE camera. Int J PIXE. 1998;8:203\u20138. https:\/\/doi.org\/10.1142\/S0129083502000160.","journal-title":"Int J PIXE"},{"key":"1782_CR14","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1142\/S0129083502000160","volume":"9","author":"A Sugimoto","year":"1999","unstructured":"Sugimoto A, Ishii K, Matsuyama S, Satoh T, Gotoh K, Yamazaki H, et al. Application of Micro-PIXE camera to elemental analysis of a single cell. Int J PIXE. 1999;9:151\u201360. https:\/\/doi.org\/10.1142\/S0129083502000160.","journal-title":"Int J PIXE"},{"key":"1782_CR15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1289\/ehp.93101302","volume":"181","author":"JL Campbell","year":"1981","unstructured":"Campbell JL, Russell SB, Faiq S, Schulte CW, Ollerhead RW, Gingerich RR. Optimization of PIXE sensitivity for biomedical applications. Nucl Inst Meth. 1981;181:285\u201392. https:\/\/doi.org\/10.1289\/ehp.93101302.","journal-title":"Nucl Inst Meth"},{"key":"1782_CR16","first-page":"701","volume":"6","author":"L Milas","year":"2000","unstructured":"Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, et al. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res. 2000;6:701\u20138.","journal-title":"Clin Cancer Res"},{"key":"1782_CR17","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1002\/ijc.10907","volume":"33","author":"CG Milross","year":"1997","unstructured":"Milross CG, Mason KA, Hunter NR, Terry NH, Patel N, Harada S, et al. Enhanced radioresponse of paclitaxel-sensitive and -resistant tumours in vivo. Eur J Cancer. 1997;33:1299\u2013308. https:\/\/doi.org\/10.1002\/ijc.10907.","journal-title":"Eur J Cancer"},{"key":"1782_CR18","doi-asserted-by":"publisher","DOI":"10.1148\/rg.2020200021","author":"JFG Marini","year":"2020","unstructured":"Marini JFG, Nunes RF, Coutinho AM, Zaniboni EC, Costa LB, Barbosa FG, Queiroz MA, Cerri GG, Cuchipigue CA. Theranostics in nuclear medicine: emerging and reemerging integrated imaging and therapies in the era of precision oncology. Radiographics. 2020. https:\/\/doi.org\/10.1148\/rg.2020200021.","journal-title":"Radiographics"},{"issue":"6","key":"1782_CR19","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/nrc2394","volume":"8","author":"K Strebhardt","year":"2008","unstructured":"Strebhardt K, Ullrich A. Paul Ehrlich\u2019s magic bullet concept: 100\u00a0years of progress. Nat Rev Cancer. 2008;8(6):473\u201380. https:\/\/doi.org\/10.1038\/nrc2394.","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"1782_CR20","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1148\/radiol.11110252","volume":"259","author":"H Hricak","year":"2011","unstructured":"Hricak H. Oncologic imaging: a guiding hand of personalized cancer care. Radiology. 2011;259(3):633\u201340. https:\/\/doi.org\/10.1148\/radiol.11110252.","journal-title":"Radiology"},{"issue":"2","key":"1782_CR21","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1148\/radiol.2017170346","volume":"286","author":"H Jadvar","year":"2018","unstructured":"Jadvar H, Chen X, Cai W, Mahmood U. Radiotheranostics in cancer diagnosis and management. Radiology. 2018;286(2):388\u2013400. https:\/\/doi.org\/10.1148\/radiol.2017170346.","journal-title":"Radiology"},{"issue":"33","key":"1782_CR22","doi-asserted-by":"publisher","first-page":"22022","DOI":"10.1074\/jbc.M109.032235","volume":"284","author":"J Mazar","year":"2009","unstructured":"Mazar J, Thomas M, Bezrukov L, Chanturia A, Pekkurnaz G, Yin S, Kuznetsov SA, Robey PG, Zimmerberg J. Cytotoxicity mediated by the Fas Ligand (FasL)-activated apoptotic pathway in stem cells*. J Biol Chem. 2009;284(33):22022\u20138. https:\/\/doi.org\/10.1074\/jbc.M109.032235.","journal-title":"J Biol Chem"},{"key":"1782_CR23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.2739\/kurumemedj.49.119","volume":"49","author":"A Akashi","year":"2002","unstructured":"Akashi A, Kuwano K. Fas-mediated lysis of target cell by IL-2 treated cytotoxic T lymphocytes. Kurume Med J. 2002;49:119\u201329.","journal-title":"Kurume Med J"},{"issue":"4","key":"1782_CR24","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1111\/j.0022-202X.2005.23657.x","volume":"124","author":"X Ni","year":"2005","unstructured":"Ni X, Chunle IZ, Talpur R, Duvic M. Resistance to activation-induced cell death and bystander cytotoxicity via the Fas\/Fas ligand pathwayare implicated in the pathogenesis of cutaneous Tcell lymphomas. J Invest Dermatol. 2005;124(4):741\u201350. https:\/\/doi.org\/10.1111\/j.0022-202X.2005.23657.x.","journal-title":"J Invest Dermatol"},{"key":"1782_CR25","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s12276-023-01136-4","volume":"56","author":"R Singh","year":"2024","unstructured":"Singh R, Kim Y-H, Lee S-J, Eom H-S, et al. 4\u20131BB immunotherapy: advances and hudles. Exp Mole Med. 2024;56:32\u20139. https:\/\/doi.org\/10.1038\/s12276-023-01136-4.","journal-title":"Exp Mole Med."},{"key":"1782_CR26","doi-asserted-by":"publisher","first-page":"e003959","DOI":"10.1136\/jitc-2021-003959","volume":"10","author":"GA Kristin","year":"2022","unstructured":"Kristin GA, Shannon KO, Breanna MB, et al. Engineering adoptive T cell therapy to co-opt FAS ligand-mediated death signaling in ovarian cancer enhances therapeutic efficacy. J Immunother Cancer. 2022;10:e003959. https:\/\/doi.org\/10.1136\/jitc-2021-003959.","journal-title":"J Immunother Cancer"},{"issue":"12","key":"1782_CR27","doi-asserted-by":"publisher","first-page":"e20191166","DOI":"10.1084\/jem.20191166","volume":"217","author":"SK Oda","year":"2020","unstructured":"Oda SK, Anderson KG, Ravikumar P, et al. A-Fas-4\u20131BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy. J Exp Med. 2020;217(12):e20191166. https:\/\/doi.org\/10.1084\/jem.20191166.","journal-title":"J Exp Med"}],"container-title":["Japanese Journal of Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11604-025-01782-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11604-025-01782-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11604-025-01782-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T11:40:13Z","timestamp":1757158813000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11604-025-01782-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":27,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["1782"],"URL":"https:\/\/doi.org\/10.1007\/s11604-025-01782-w","relation":{},"ISSN":["1867-1071","1867-108X"],"issn-type":[{"type":"print","value":"1867-1071"},{"type":"electronic","value":"1867-108X"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"assertion":[{"value":"16 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no conflicts of interest directly relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}