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Development of an α-synuclein positron emission tomography tracer for imaging synucleinopathies.
Xiang, Jie; Tao, Youqi; Xia, Yiyuan; Luo, Shilin; Zhao, Qinyue; Li, Bowei; Zhang, Xiaoqian; Sun, Yunpeng; Xia, Wencheng; Zhang, Mingming; Kang, Seong Su; Ahn, Eun-Hee; Liu, Xia; Xie, Fang; Guan, Yihui; Yang, Jenny J; Bu, Lihong; Wu, Shengxi; Wang, Xiaochuan; Cao, Xuebing; Liu, Cong; Zhang, Zhentao; Li, Dan; Ye, Keqiang.
Afiliação
  • Xiang J; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurobiology, Fourth Military Medical University, Xi'an, China.
  • Tao Y; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Xia Y; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Biomedical Sciences, School of Medicine, JiangHan University,
  • Luo S; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, China.
  • Zhao Q; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Li B; Shenzhen Institute of Advanced Technology, University of Chinese Academy of Science, Shenzhen, Guangdong 518055, China.
  • Zhang X; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China.
  • Sun Y; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Xia W; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Zhang M; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Kang SS; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Ahn EH; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Liu X; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Xie F; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
  • Guan Y; Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
  • Yang JJ; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
  • Bu L; PET-CT/MRI Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
  • Wu S; Department of Neurobiology, Fourth Military Medical University, Xi'an, China.
  • Wang X; Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Cao X; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China.
  • Liu C; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
  • Zhang Z; Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: zhentaozhang@whu.edu.cn.
  • Li D; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: lidan2017@sjtu
  • Ye K; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China. Electronic address: kq.ye@siat.ac.cn.
Cell ; 186(16): 3350-3367.e19, 2023 08 03.
Article em En | MEDLINE | ID: mdl-37421950
ABSTRACT
Synucleinopathies are characterized by the accumulation of α-synuclein (α-Syn) aggregates in the brain. Positron emission tomography (PET) imaging of synucleinopathies requires radiopharmaceuticals that selectively bind α-Syn deposits. We report the identification of a brain permeable and rapid washout PET tracer [18F]-F0502B, which shows high binding affinity for α-Syn, but not for Aß or Tau fibrils, and preferential binding to α-Syn aggregates in the brain sections. Employing several cycles of counter screenings with in vitro fibrils, intraneuronal aggregates, and neurodegenerative disease brain sections from several mice models and human subjects, [18F]-F0502B images α-Syn deposits in the brains of mouse and non-human primate PD models. We further determined the atomic structure of the α-Syn fibril-F0502B complex by cryo-EM and revealed parallel diagonal stacking of F0502B on the fibril surface through an intense noncovalent bonding network via inter-ligand interactions. Therefore, [18F]-F0502B is a promising lead compound for imaging aggregated α-Syn in synucleinopathies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Sinucleinopatias Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Sinucleinopatias Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China