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Preclinical Evaluation of Novel Positron Emission Tomography (PET) Probes for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2).
Chen, Zhen; Chen, Jiahui; Mori, Wakana; Yi, Yongjia; Rong, Jian; Li, Yinlong; Leon, Erick R Calderon; Shao, Tuo; Song, Zhendong; Yamasaki, Tomoteru; Ishii, Hideki; Zhang, Yiding; Kokufuta, Tomomi; Hu, Kuan; Xie, Lin; Josephson, Lee; Van, Richard; Shao, Yihan; Factor, Stewart; Zhang, Ming-Rong; Liang, Steven H.
Affiliation
  • Chen Z; Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, International Innovation Center for Forest Chemicals and Material
  • Chen J; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • Mori W; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Rd, Atlanta, Georgia 30322, United States.
  • Yi Y; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • Rong J; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Li Y; Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, International Innovation Center for Forest Chemicals and Material
  • Leon ERC; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Rd, Atlanta, Georgia 30322, United States.
  • Shao T; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • Song Z; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Rd, Atlanta, Georgia 30322, United States.
  • Yamasaki T; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • Ishii H; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
  • Zhang Y; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • Kokufuta T; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Rd, Atlanta, Georgia 30322, United States.
  • Hu K; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Xie L; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Josephson L; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Van R; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Shao Y; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Factor S; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
  • Zhang MR; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • Liang SH; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
J Med Chem ; 67(4): 2559-2569, 2024 02 22.
Article in En | MEDLINE | ID: mdl-38305157
ABSTRACT
Parkinson's disease (PD) is one of the most highly debilitating neurodegenerative disorders, which affects millions of people worldwide, and leucine-rich repeat kinase 2 (LRRK2) mutations have been involved in the pathogenesis of PD. Developing a potent LRRK2 positron emission tomography (PET) tracer would allow for in vivo visualization of LRRK2 distribution and expression in PD patients. In this work, we present the facile synthesis of two potent and selective LRRK2 radioligands [11C]3 ([11C]PF-06447475) and [18F]4 ([18F]PF-06455943). Both radioligands exhibited favorable brain uptake and specific bindings in rodent autoradiography and PET imaging studies. More importantly, [18F]4 demonstrated significantly higher brain uptake in the transgenic LRRK2-G2019S mutant and lipopolysaccharide (LPS)-injected mouse models. This work may serve as a roadmap for the future design of potent LRRK2 PET tracers.
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Full text: 1 Database: MEDLINE Main subject: Parkinson Disease / Pyrimidines / Morpholines / Nitriles Limits: Animals / Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2024 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Parkinson Disease / Pyrimidines / Morpholines / Nitriles Limits: Animals / Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2024 Type: Article