Synthesis and preliminary evaluation of 4-hydroxy-6-(3-[11C]methoxyphenethyl)pyridazin-3(2H)-one,a 11C-labeled d-amino acid oxidase (DAAO) inhibitor for PET imaging |
| |
| Affiliation: | 1. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States;2. Department of Radiopharmaceutics Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan;3. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, United States;4. Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell’Insubria, Varese 21100, Italy;1. Chemistry Department, Faculty of Science, Fayoum University, Fayoum, Egypt;2. Central European Institute of Technology (CEITEC), Brno University of Technology, Purkyňova 464/118, 612 00 Brno, Czech Republic;3. Brno University of Technology, Faculty of Chemistry, Institute of Physical and Applied Chemistry, Purkyňova 464/118, 612 00 Brno, Czech Republic;4. Petrochemical Research Chair, Chemistry Department, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia;5. Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt;6. Textile Research Division, National Research Center, Dokki, PO Box 12622, Giza 12522, Egypt;1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China;2. ChengDu Military General Hospital, Chengdu 610083, PR China;1. Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan;2. SHI Accelerator Service Co. Ltd, 5-9-11 Kitashinagawa, Shinagawa-ku, Tokyo 141-8686, Japan;1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China;2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China |
| |
| Abstract: | Selective DAAO inhibitors have demonstrated promising therapeutic effects in clinical studies, including clinically alleviating symptoms of schizophrenic patients and ameliorating cognitive function in Alzheimer’s patients with early phase. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography ligand based on a DAAO inhibitor, DAO-1903 (8). 11C-Isotopologue of 8 was prepared in high radiochemical yield with high radiochemical purity (>99%) and high molar activity (>37 GBq/µmol). In vitro autoradiography studies indicated that the ligand possessed high in vitro specific binding to DAAO, while in vivo dynamic PET studies demonstrated that [11C]8 failed to cross the blood–brain barrier possibly due to moderate brain efflux mechanism. Further chemical scaffold optimization is necessary to overcome limited brain permeability and improve specific binding. |
| |
| Keywords: | Carbon-11 Positron emission tomography (PET) Cerebellum function Schizophrenia |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
