Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1). Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Lee, Boeun; Kim, Yu Kyeong; Lee, Ji Youn; Kim, Young Joo; Lee, Yun-Sang; Lee, Dong Soo; Chung, June-Key; Jeong, Jae Min
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 37:Issue 6(2017)
• Page Start: 2283
• Page End: 2293
• Publication Date: 2017-06
• Subjects: Autoradiography -- metabotropic glutamate receptor subtype 1 (mGluR1) -- positron emission tomography (PET) -- [18F]cEFQ; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X16663948
• Languages: English
• ISSNs: 0271-678X

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 [ 18 F]cEFQ (3-ethyl-2-[ 18 F]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 [ 18 F]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, [ 18 F]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 [ 18 F]cEFQ. However, the uptake was not blocked by pre-treatment with the mGluR5-specific antagonist ABP688. The trans isomer [ 18 F]tEFQ did not show high uptake in the mGluR1-rich region. [ 18 F]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.