Your browser doesn't support javascript.
loading
Synthesis and Preliminary Evaluation of [11 C]GNE-1023 as a Potent PET Probe for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2) in Parkinson's Disease.
Chen, Zhen; Shao, Tuo; Gao, Wei; Fu, Hualong; Collier, Thomas Lee; Rong, Jian; Deng, Xiaoyun; Yu, Qingzhen; Zhang, Xiaofei; Davenport, April T; Daunais, James B; Wey, Hsiao-Ying; Shao, Yihan; Josephson, Lee; Qiu, Wen-Wei; Liang, Steven.
Afiliação
  • Chen Z; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Shao T; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Gao W; Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
  • Fu H; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Collier TL; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Rong J; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Deng X; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Yu Q; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Zhang X; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Davenport AT; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, 27157, USA.
  • Daunais JB; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, 27157, USA.
  • Wey HY; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Shao Y; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA.
  • Josephson L; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Qiu WW; Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
  • Liang S; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
ChemMedChem ; 14(17): 1580-1585, 2019 09 04.
Article em En | MEDLINE | ID: mdl-31365783
ABSTRACT
Leucine-rich repeat kinase 2 (LRRK2) is a large protein involved in the pathogenesis of Parkinson's disease (PD). It has been demonstrated that PD is mainly conferred by LRRK2 mutations that bring about increased kinase activity. As a consequence, selective inhibition of LRRK2 may help to recover the normal functions of LRRK2, thereby serving as a promising alternative therapeutic target for PD treatment. The mapping of LRRK2 by positron emission tomography (PET) studies allows a thorough understanding of PD and other LRRK2-related disorders; it also helps to validate and translate novel LRRK2 inhibitors. However, no LRRK2 PET probes have yet been reported in the primary literature. Herein we present a facile synthesis and preliminary evaluation of [11 C]GNE-1023 as a novel potent PET probe for LRRK2 imaging in PD. [11 C]GNE-1023 was synthesized in good radiochemical yield (10 % non-decay-corrected RCY), excellent radiochemical purity (>99 %), and high molar activity (>37 GBq µmol-1 ). Excellent in vitro binding specificity of [11 C]GNE-1023 toward LRRK2 was demonstrated in cross-species studies, including rat and nonhuman primate brain tissues by autoradiography experiments. Subsequent whole-body biodistribution studies indicated limited brain uptake and urinary and hepatobiliary elimination of this radioligand. This study may pave the way for further development of a new generation of LRRK2 PET probes.
Assuntos
Palavras-chave
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: Doença de Parkinson / Pirimidinas / Morfolinas / Compostos Radiofarmacêuticos / Inibidores de Proteínas Quinases / Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina Limite: Animals / Female / Humans Idioma: En Revista: ChemMedChem Assunto da revista: FARMACOLOGIA / QUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
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: Doença de Parkinson / Pirimidinas / Morfolinas / Compostos Radiofarmacêuticos / Inibidores de Proteínas Quinases / Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina Limite: Animals / Female / Humans Idioma: En Revista: ChemMedChem Assunto da revista: FARMACOLOGIA / QUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos