{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:18:11Z","timestamp":1788351491013,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD025234"],"award-info":[{"award-number":["S10OD025234"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The sigma\u20101 receptor (\u03c31R) is a stress\u2010activated chaperone protein that has emerged as a significant therapeutic target for neurodegenerative disorders. Developing effective positron emission tomography (PET) imaging probes targeting \u03c31R is crucial for visualizing its distribution and function in the brain, as well as facilitating related drug development. In this study, two novel <jats:sup>11<\/jats:sup>C\u2010labeled PET probes based on the structure of a potent \u03c31R ligand Lan\u20100101 are designed and synthesized. PET imaging studies in mice reveal that [<jats:sup>11<\/jats:sup>C]CNY\u201001 exhibits good brain uptake and binding specificity. Subsequent evaluation in non\u2010human primates further demonstrates that [<jats:sup>11<\/jats:sup>C]CNY\u201001 displays favorable brain penetration, slow clearance kinetics, and characteristics of irreversible binding to its target in blockage experiments. To assess the clinical potential of the probe, both in vitro experiments and in vivo PET imaging using [<jats:sup>11<\/jats:sup>C]CNY\u201001 are conducted in Alzheimer's disease (AD) transgenic mouse models. These studies reveal a significant decrease in \u03c31R expression in the brain under conditions of AD amyloid pathology and microglial activation, highlighting the probe's sensitivity to disease\u2010related receptor changes. This work establishes [<jats:sup>11<\/jats:sup>C]CNY\u201001 as a promising tool for investigating the relationship between \u03c31R and neurological disorders, potentially advancing the understanding of \u03c31R's role in disease pathophysiology and therapeutic interventions.<\/jats:p>","DOI":"10.1002\/advs.202414827","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T13:44:22Z","timestamp":1744897462000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of Carbon\u201011 Labeled Pyrimidine Derivatives as Novel Positron Emission Tomography (PET) Agents Enabling Brain Sigma\u20101 Receptor Imaging"],"prefix":"10.1002","volume":"12","author":[{"given":"Ping","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Targeted Tracer Research and Development Laboratory West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Institute of Respiratory Health Targeted Tracer Research and Development Laboratory Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Precision Medicine Center Precision Medicine Key Laboratory of Sichuan Province West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"The Research Units of West China Chinese Academy of Medical Sciences West China Hospital  Chengdu Sichuan 610041 China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Gomm","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School  114 16th Street Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Hyeon","family":"Yoo","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital Harvard Medical School  Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasenjit","family":"Mondal","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School  114 16th Street Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleur Marie","family":"Lobo","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School  114 16th Street Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Targeted Tracer Research and Development Laboratory West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Institute of Respiratory Health Targeted Tracer Research and Development Laboratory Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Precision Medicine Center Precision Medicine Key Laboratory of Sichuan Province West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"The Research Units of West China Chinese Academy of Medical Sciences West China Hospital  Chengdu Sichuan 610041 China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Targeted Tracer Research and Development Laboratory West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Institute of Respiratory Health Targeted Tracer Research and Development Laboratory Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Precision Medicine Center Precision Medicine Key Laboratory of Sichuan Province West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"The Research Units of West China Chinese Academy of Medical Sciences West China Hospital  Chengdu Sichuan 610041 China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Targeted Tracer Research and Development Laboratory West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Institute of Respiratory Health Targeted Tracer Research and Development Laboratory Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Precision Medicine Center Precision Medicine Key Laboratory of Sichuan Province West China Hospital Sichuan University  Chengdu Sichuan 610041 China"},{"name":"The Research Units of West China Chinese Academy of Medical Sciences West China Hospital  Chengdu Sichuan 610041 China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao\u2010Ying","family":"Wey","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital Harvard Medical School  Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph E.","family":"Tanzi","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School  114 16th Street Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital Harvard Medical School  114 16th Street Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2076-4193","authenticated-orcid":false,"given":"Changning","family":"Wang","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital Harvard Medical School  Charlestown MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Renmin Hospital of Wuhan University  Wuhan Hubei 430060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.036"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)30536-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)91326-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.8072"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.2.491"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00050"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.02.035"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1451-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2010.11.016"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.10.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12149-007-0094-z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.11.010"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109134"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk1051"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.145351"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00699-9"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.10.006"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12129"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm3007323"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00314"},{"key":"e_1_2_8_21_1","first-page":"11","author":"Rosen D. A.","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955705774329519"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2017-0164"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2019.172796"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-017-0572-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.005835"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0204rev"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(00)00081-0"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-015-0122-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(01)00011-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2007.03.009"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300371c"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S167839"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.117.192641"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501207r"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17391"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(96)00161-X"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar500233s"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)20023-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01292615"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00014-2"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-1920-9"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.07.002"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2025.108993"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.2c00466"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16020194"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2008.04.010"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02985120"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91441-T"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300677110"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.6b00288"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2013.07.001"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01491"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CC03785H"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.05.017"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107279"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2012.00027"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c04824"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(00)00137-2"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c02178"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan8821"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201923"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202414827","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:44:19Z","timestamp":1759743859000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202414827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":62,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/advs.202414827"],"URL":"https:\/\/doi.org\/10.1002\/advs.202414827","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"assertion":[{"value":"2024-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2414827"}}