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A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network.
Cheng, Ran; Fujinaga, Masayuki; Yang, Jing; Rong, Jian; Haider, Ahmed; Ogasawara, Daisuke; Van, Richard S; Shao, Tuo; Chen, Zhen; Zhang, Xiaofei; Calderon Leon, Erick R; Zhang, Yiding; Mori, Wakana; Kumata, Katsushi; Yamasaki, Tomoteru; Xie, Lin; Sun, Shaofa; Wang, Lu; Ran, Chongzhao; Shao, Yihan; Cravatt, Benjamin; Josephson, Lee; Zhang, Ming-Rong; Liang, Steven H.
Affiliation
  • Cheng R; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Fujinaga M; School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China.
  • Yang J; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.
  • Rong J; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02125, USA.
  • Haider A; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Ogasawara D; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Van RS; The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Shao T; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA.
  • Chen Z; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Zhang X; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Calderon Leon ER; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Zhang Y; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA.
  • Mori W; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.
  • Kumata K; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.
  • Yamasaki T; 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.
  • Sun S; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.
  • Wang L; Hubei Collaborative Innovation Centre for Non-power Nuclear Technology, College of Nuclear Technology & Chemistry and Biology, Hubei University of Science and Technology, Xianning, Hubei Province, 437100, China.
  • Ran C; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Shao Y; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02125, USA.
  • Cravatt B; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA.
  • Josephson L; The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Zhang MR; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Liang SH; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan. zhang.ming-rong@qst.go.jp.
Acta Pharmacol Sin ; 43(11): 3002-3010, 2022 Nov.
Article de En | MEDLINE | ID: mdl-35513432
ABSTRACT
Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [18F]FEPAD. Pharmacokinetics and binding studies on [18F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [18F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Endocannabinoïdes / Acylglycerol lipase Langue: En Journal: Acta Pharmacol Sin Sujet du journal: FARMACOLOGIA Année: 2022 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Endocannabinoïdes / Acylglycerol lipase Langue: En Journal: Acta Pharmacol Sin Sujet du journal: FARMACOLOGIA Année: 2022 Type de document: Article Pays d'affiliation: États-Unis d'Amérique