방사선의학 웹진

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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.

Author information

Lee B1,2, Kim YK1,3, Lee JY1,4,5, Kim YJ1,4, Lee YS1,2, Lee DS1,2, Chung JK1,4, Jeong JM1,4,5.

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.

3 Department of Nuclear Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University, 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.