{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:19:58Z","timestamp":1788164398167,"version":"build-2803163510"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202214"],"award-info":[{"award-number":["82202214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202216"],"award-info":[{"award-number":["82202216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["XDA0580000"],"award-info":[{"award-number":["XDA0580000"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011488","name":"Health and Family Planning Committee of Pudong New Area","doi-asserted-by":"publisher","award":["PW2023B-15"],"award-info":[{"award-number":["PW2023B-15"]}],"id":[{"id":"10.13039\/501100011488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Shanghai Institute of Applied Physics, Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["SINAP-QYJS-202401"],"award-info":[{"award-number":["SINAP-QYJS-202401"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Targeted alpha therapy (TAT) with Astatine-211 (211At) has shown potent antitumor efficacy, yet free 211At released through deastatination accumulates in the thyroid via the sodium\u2013iodide symporter (NIS), posing safety concerns distinct from \u03b2-emitter counterparts such as 131I. Here, we combine multimodal in vivo imaging and molecular profiling to resolve the kinetics\u2013toxicity relationship of 211At- versus 131I-induced thyroid injury. Using serial 99mTcO4\u2013 SPECT\/CT and 18F-FDG PET\/CT, we captured the dynamic evolution of thyroid function and metabolic inflammation in BALB\/c mice receiving equipotent cytotoxic doses of Na131I (18.5 MBq), low-dose Na211At (18.5 kBq), or high-dose Na211At (92.5 kBq). Biodistribution study revealed rapid NIS-mediated uptake of 211At peaking at 7 h and complete clearance by 44 h, yet subsequent SPECT and hormonal analyses demonstrated progressive thyroidal dysfunction independent of residual activity. PET-based metabolic imaging confirmed persistent inflammatory stress despite radionuclide clearance. By integrating multimodal spatiotemporal imaging, cytokine profiling, RNA sequencing, and immune deconvolution techniques, we identified fundamental distinctions between \u03b1 and \u03b2 irradiation in immunopathological mechanisms. While \u03b2 irradiation predominantly elicited transient innate immune activation, high-LET \u03b1-particle exposure preferentially shifted the thyroid immune landscape toward an antigen-experienced adaptive state. This immune remodeling may contribute to the persistence of thyroidal dysfunction and inflammatory stress following \u03b1-particle exposure, even after radionuclide clearance. This spatiotemporal imaging framework provides a mechanistic basis for understanding \u03b1-induced organ injury, challenges dose-centric safety models, and guides the design and monitoring of future TAT regimens.<\/jats:p>","DOI":"10.1021\/cbmi.6c00023","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T11:34:24Z","timestamp":1773142464000},"page":"1827-1836","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Imaging\nDynamics and Divergent Immune\nMechanisms of 211At- Versus 131I-Induced\nThyroid Injury"],"prefix":"10.1021","volume":"4","author":[{"given":"Jiajun","family":"Liu","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong University School of Medicine , , ,","place":["Shanghai, China, 200025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0123-4118","authenticated-orcid":true,"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Applied Physics, Chinese Academy of Sciences , ,","place":["Shanghai, China, 201800"]},{"name":"Shanghai Changhai Hospital , , ,","place":["Shanghai, China, 200433"]},{"name":"Fudan University Pudong Medical Center , , ,","place":["Shanghai, China, 201399"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2150-1939","authenticated-orcid":true,"given":"Shuai","family":"Xue","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Applied Physics, Chinese Academy of Sciences , ,","place":["Shanghai, China, 201800"]},{"name":"Fudan University Pudong Medical Center , , ,","place":["Shanghai, China, 201399"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitong","family":"Hou","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2835-8066","authenticated-orcid":true,"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2051-766X","authenticated-orcid":true,"given":"Changjing","family":"Zuo","sequence":"additional","affiliation":[{"name":"Shanghai Changhai Hospital , , ,","place":["Shanghai, China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengling","family":"Shan","sequence":"additional","affiliation":[{"name":"Fudan University Pudong Medical Center , , ,","place":["Shanghai, China, 201399"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Cai","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University School of Medicine , , ,","place":["Shanghai, China, 200025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-2803","authenticated-orcid":true,"given":"Danni","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Applied Physics, Chinese Academy of Sciences , ,","place":["Shanghai, China, 201800"]},{"name":"Shanghai Changhai Hospital , , ,","place":["Shanghai, China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"2026083104113588600_cit1","doi-asserted-by":"publisher","first-page":"1076210","DOI":"10.3389\/fmed.2022.1076210","article-title":"Astatine-211 Based\nRadionuclide Therapy: Current Clinical Trial Landscape","volume":"9","author":"Albertsson","year":"2023","journal-title":"Front. Med."},{"issue":"1","key":"2026083104113588600_cit2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.2967\/jnumed.107.046938","article-title":"Clinical\nExperience with \u03b1-Particle\u2013Emitting 211At:\nTreatment of Recurrent Brain Tumor Patients with 211At-Labeled\nChimeric Antitenascin Monoclonal Antibody 81C6","volume":"49","author":"Zalutsky","year":"2008","journal-title":"J. Nucl. Med."},{"issue":"7","key":"2026083104113588600_cit3","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.2967\/jnumed.109.062604","article-title":"Intraperitoneal\n\u03b1-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics\nand Dosimetry of 211At-MX35 F(Ab\u2032)2 \u2500a\nPhase I Study","volume":"50","author":"Andersson","year":"2009","journal-title":"J. Nucl. Med."},{"issue":"3","key":"2026083104113588600_cit4","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.1016\/S2666-6367(21)00083-X","article-title":"A Phase I\nTrial of First-in-Human Alpha-Emitter Astatine-211-Labeled Anti-CD45\nAntibody (211At-BC8-B10) in Combination with Fludarabine\nand TBI As Conditioning for Allogeneic Hematopoietic Cell Transplantation\n(HCT) for Patients with Refractory\/Relapsed Leukemia or High-Risk\nMyelodysplastic Syndrome (MDS): Preliminary Results of Dose Escalation","volume":"27","author":"Sandmaier","year":"2021","journal-title":"Transplant. Cell Ther."},{"issue":"6","key":"2026083104113588600_cit5","doi-asserted-by":"publisher","first-page":"738","DOI":"10.3390\/pharmaceutics16060738","article-title":"The Different Strategies for the Radiolabeling of [211At]-Astatinated Radiopharmaceuticals","volume":"16","author":"Gao","year":"2024","journal-title":"Pharmaceutics"},{"issue":"1","key":"2026083104113588600_cit6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s41181-024-00298-4","article-title":"Astatine-211\nRadiolabelling Chemistry:\nFrom Basics to Advanced Biological Applications","volume":"9","author":"Vanermen","year":"2024","journal-title":"EJNMMI Radiopharm. Chem."},{"issue":"7","key":"2026083104113588600_cit7","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.2967\/jnumed.108.061150","article-title":"Radiation-Induced\nThyroid Stunning: Differential Effects\nof 123 I, 131I, 99mTc, and 211At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid\nCells","volume":"50","author":"Lundh","year":"2009","journal-title":"J. Nucl. Med."},{"issue":"2","key":"2026083104113588600_cit8","doi-asserted-by":"publisher","first-page":"767","DOI":"10.7150\/thno.79806","article-title":"Radiopharmaceuticals Heat Anti-Tumor\nImmunity","volume":"13","author":"Sun","year":"2023","journal-title":"Theranostics"},{"key":"2026083104113588600_cit9","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.2967\/jnumed.125.270810","article-title":"First-in-Human\nStudy of [211At]NaAt as Targeted\n\u03b1-Therapy in Patients with Radioiodine-Refractory Thyroid Cancer\n(Alpha-T1 Trial)","volume":"66","author":"Watabe","year":"2025","journal-title":"J. Nucl. Med."},{"issue":"1","key":"2026083104113588600_cit10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1039\/D3MD00579H","article-title":"In Vivo Stability\nof 211At-Radiopharmaceuticals: On the Impact of Halogen\nBond Formation","volume":"15","author":"Yssartier","year":"2024","journal-title":"RSC Med. Chem."},{"issue":"3","key":"2026083104113588600_cit11","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1089\/thy.2022.0275","article-title":"Discoveries in Thyroid\nAutoimmunity in the Past Century","volume":"33","author":"McLachlan","year":"2023","journal-title":"Thyroid"},{"key":"2026083104113588600_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2018.03.007","article-title":"Hematologic Toxicity\nfrom Radium-223 Therapy for Bone Metastases in Castration-Resistant\nProstate Cancer: Risk Factors and Practical Considerations","volume":"16","author":"Jacene","year":"2018","journal-title":"Clin. Genitourin Cancer"},{"key":"2026083104113588600_cit13","doi-asserted-by":"publisher","first-page":"129364","DOI":"10.1016\/j.ijbiomac.2024.129364","article-title":"A Sodium Alginate Intervention\nStrategy to Enhance Therapeutic Effects of Bone-Targeted Alpha Therapy\nvia Remodeling 223RaCl2 Distribution","volume":"260","author":"Xue","year":"2024","journal-title":"Int. J.\nBiol. Macromol."},{"issue":"4","key":"2026083104113588600_cit14","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.1021\/acs.jmedchem.4c02281","article-title":"An 211At-Labeled Tetrazine\nfor Pretargeted Therapy","volume":"68","author":"Herth","year":"2025","journal-title":"J. Med. Chem."},{"issue":"4","key":"2026083104113588600_cit15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.2967\/jnumed.123.267043","article-title":"Development\nand Preclinical Evaluation of [211At]PSAt-3-Ga: An Inhibitor\nfor Targeted \u03b1-Therapy of Prostate Cancer","volume":"65","author":"El Fakiri","year":"2024","journal-title":"J. Nucl. Med."},{"issue":"1","key":"2026083104113588600_cit16","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s40658-020-00326-7","article-title":"Human Dosimetry of Free 211At and Meta-[211At]Astatobenzylguanidine (211At-MABG) Estimated Using\nPreclinical Biodistribution from Normal Mice","volume":"7","author":"Ukon","year":"2020","journal-title":"EJNMMI Phys."},{"issue":"3","key":"2026083104113588600_cit17","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1007\/s00259-022-06016-z","article-title":"Targeted \u03b1-Therapy\nUsing Astatine (211At)-Labeled PSMA1, 5, and 6: A Preclinical\nEvaluation as a Novel Compound","volume":"50","author":"Watabe","year":"2023","journal-title":"Eur. J. Nucl.\nMed. Mol. Imaging"},{"issue":"16","key":"2026083104113588600_cit18","doi-asserted-by":"publisher","first-page":"9434","DOI":"10.3390\/ijms23169434","article-title":"Comparison of the Therapeutic\nEffects of [211At]NaAt and [131I]NaI in an NIS-Expressing\nThyroid Cancer Mouse Model","volume":"23","author":"Watabe","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026083104113588600_cit19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s00259-025-07390-0","article-title":"Targeted Alpha\nTherapy: A Comprehensive Analysis of the Biological Effects from \u201cLocal-Regional-Systemic\u201d\nDimensions","volume":"53","author":"Song","year":"2025","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"issue":"3","key":"2026083104113588600_cit20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s42000-020-00178-x","article-title":"Detection\nof Thyroiditis on PET\/CT Imaging: A Systematic Review","volume":"19","author":"Albano","year":"2020","journal-title":"Hormones"},{"issue":"1","key":"2026083104113588600_cit21","doi-asserted-by":"publisher","DOI":"10.1530\/ETJ-22-0165","article-title":"Significance\nof FDG\u2013PET\nStandardized Uptake Values in Predicting Thyroid Disease","volume":"12","author":"Kikuchi","year":"2023","journal-title":"Eur. Thyroid J."},{"issue":"6","key":"2026083104113588600_cit22","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1667\/RR3031.1","article-title":"Cytokines\nin Radiobiological Responses:\nA Review","volume":"178","author":"Schaue","year":"2012","journal-title":"Radiat. Res."},{"issue":"1","key":"2026083104113588600_cit23","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12950-015-0058-3","article-title":"Portrait of\nInflammatory Response to Ionizing Radiation Treatment","volume":"12","author":"Di Maggio","year":"2015","journal-title":"J. Inflamm."},{"key":"2026083104113588600_cit24","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1038\/s41467-026-68834-1","article-title":"Priming\nversus Propagating: Distinct Immune Effects of Alpha- versus Beta-Particle\nEmitting Radiopharmaceuticals When Combined with Immune Checkpoint\nInhibition in Mice","volume":"17","author":"Kerr","year":"2026","journal-title":"Nat. Commun."},{"issue":"1","key":"2026083104113588600_cit25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13044-025-00254-7","article-title":"Challenges\nin Subtyping Disease Entities of Thyroid Dysfunction Following Combined\nImmune Checkpoint Inhibitor Therapy: A Case Report","volume":"18","author":"Thomsen","year":"2025","journal-title":"Thyroid Res."},{"key":"2026083104113588600_cit26","doi-asserted-by":"publisher","first-page":"1495946","DOI":"10.3389\/fimmu.2024.1495946","article-title":"Evaluating\nthe Influence of Anti-PD-1\nImmunotherapy Combined with IMRT on Thyroid Dysfunction in Nasopharyngeal\nCarcinoma","volume":"15","author":"Chen","year":"2025","journal-title":"Front. Immunol."}],"container-title":["Chemical &amp; Biomedical\nImaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cbmi.6c00023","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article-pdf\/4\/8\/1827\/66262000\/cbmi.6c00023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article-pdf\/4\/8\/1827\/66262000\/cbmi.6c00023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:11:45Z","timestamp":1788163905000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article\/4\/8\/1827\/5232848\/Spatiotemporal-Imaging-Dynamics-and-Divergent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,3,9]]},"published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1021\/cbmi.6c00023","relation":{},"ISSN":["2832-3637"],"issn-type":[{"value":"2832-3637","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}