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Development of a New Positron Emission Tomography Imaging Radioligand Targeting RIPK1 in the Brain and Characterization in Alzheimer's Disease.
Bai, Ping; Lan, Yu; Liu, Yan; Mondal, Prasenjit; Gomm, Ashley; Xu, Yulong; Wang, Yanli; Wang, Yongle; Kang, Leyi; Pan, Lili; Bagdasarian, Frederick A; Hallisey, Madelyn; Lobo, Fleur; Varela, Breanna; Choi, Se Hoon; Gomperts, Stephen N; Wey, Hsiao-Ying; Shen, Shiqian; Tanzi, Rudolph E; Wang, Changning; Zhang, Can.
Afiliação
  • Bai P; Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, We
  • Lan Y; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Liu Y; Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Mondal P; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Gomm A; Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA.
  • Xu Y; Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA.
  • Wang Y; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Wang Y; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Kang L; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Pan L; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Bagdasarian FA; Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Hallisey M; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Lobo F; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Varela B; Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, We
  • Choi SH; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Gomperts SN; Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA.
  • Wey HY; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA.
  • Shen S; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Tanzi RE; Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
  • Wang C; Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA.
  • Zhang C; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Adv Sci (Weinh) ; 11(32): e2309021, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38923244
ABSTRACT
Targeting receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY-10 is reported, which may enable brain RIPK1 imaging. [11C]CNY-10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY-10 is characterized by PET imaging in rodents and a non-human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY-10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY-10-based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY-10 for AD and potentially other RIPK1-related human studies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Tomografia por Emissão de Pósitrons / Proteína Serina-Treonina Quinases de Interação com Receptores / Doença de Alzheimer Limite: Animals / Female / Humans / Male Idioma: En Revista: Adv Sci (Weinh) Ano de publicação: 2024 Tipo de documento: Article País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Tomografia por Emissão de Pósitrons / Proteína Serina-Treonina Quinases de Interação com Receptores / Doença de Alzheimer Limite: Animals / Female / Humans / Male Idioma: En Revista: Adv Sci (Weinh) Ano de publicação: 2024 Tipo de documento: Article País de publicação: Alemanha