title: Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1).
abstract: Metabotropic glutamate receptor type 1 (mGluR1) is related with various neurological and psychiatric diseases, such as anxiety, depression, epilepsy, Parkinson's disease, and neuropathic pain. Hence, mGluR1 is an important target for drug development and imaging. We synthesized [18F]cEFQ (3-ethyl-2-[18F]fluoroquinolin-6-yl cis-(4-methoxycyclohexyl)methanone) as a PET tracer for selective mGluR1 imaging and evaluated its properties in rodents. A chloroquinoline precursor was labeled by a nucleophilic substitution reaction, and the resulting [18F]cEFQ was obtained with high radiochemical purity (>99%) and specific activity (63-246 GBq/µmol). The log D value was 3.24, and the initial brain uptake at 10 min was over 4% of injected dose per gram in BALB/c mice. According to PET/CT and autoradiography in SD rats, [18F]cEFQ showed wide distribution in the whole brain and the highest uptake in the cerebellum. Pre-treatment with unlabeled cEFQ or the mGluR1-specific antagonist JNJ16259685 blocked the uptake of [18F]cEFQ. However, the uptake was not blocked by pre-treatment with the mGluR5-specific antagonist ABP688. The trans isomer [18F]tEFQ did not show high uptake in the mGluR1-rich region. [18F]cEFQ was straightforwardly prepared using a chloro-derivative precursor. Its feasibility as a specific and selective PET agent for imaging mGluR1 was proved by in vitro and in vivo experiments using rodents.
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors: Boeun
authors: B
authors: Lee
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|3 Department of Nuclear Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University, Seoul, Republic of Korea.
authors: Yu Kyeong
authors: YK
authors: Kim
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|5 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
authors: Ji Youn
authors: JY
authors: Lee
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Young Joo
authors: YJ
authors: Kim
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors: Yun-Sang
authors: YS
authors: Lee
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors: Dong Soo
authors: DS
authors: Lee
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: June-Key
authors: JK
authors: Chung
authors: 1 Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|5 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
authors: Jae Min
authors: JM
authors: Jeong
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D008297:Male; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: C000621814:3-ethyl-2-fluoroquinolin-6-yl (4-methoxycyclohexyl)methanone; D011804:Quinolines; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
keywords: Autoradiography; [18F]cEFQ; metabotropic glutamate receptor subtype 1 (mGluR1); positron emission tomography (PET)