Synthesis and evaluation of 6-[1-(2-[18F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain

• Published in: Bioorganic & medicinal chemistry 2011-01, Vol.19 (1), p.102-110
• Main Authors: Fujinaga, Masayuki, Yamasaki, Tomoteru, Kawamura, Kazunori, Kumata, Katsushi, Hatori, Akiko, Yui, Joji, Yanamoto, Kazuhiko, Yoshida, Yuichiro, Ogawa, Masanao, Nengaki, Nobuki, Maeda, Jun, Fukumura, Toshimitsu, Zhang, Ming-Rong
• Format: Article
• Language: English
• Subjects: [18F]FPTQ; Animals; Autoradiography; Biological and medical sciences; Brain - diagnostic imaging; cerebellum; chemistry; Contrast media. Radiopharmaceuticals; fluorine; glutamic acid; image analysis; Magnetic Resonance Imaging; Medical sciences; metabolites; Metabotropic glutamate receptor type 1; PET; Pharmacology. Drug treatments; Positron-Emission Tomography; potassium; quinoline; Quinolines - metabolism; radiolabeling; Radiopharmaceuticals - metabolism; Rats; Receptors, Metabotropic Glutamate - metabolism; Tissue Distribution; Triazoles - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.11.048

The purpose of this study was to synthesize 6-[1-(2-[18F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline ([18F]FPTQ, [18F]7a) and to evaluate its potential as a positron emission tomography ligand for imaging metabotropic glutamate receptor type 1 (mGluR1) in the rat brain. Compound [18F]7a was synthesized by [18F]fluorination of 6-[1-(2-bromo-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline (7b) with potassium [18F]fluoride. At the end of synthesis, 1280–1830MBq (n=8) of [18F]7a was obtained with >98% radiochemical purity and 118–237GBq/μmol specific activity using 3300–4000MBq of [18F]F−. In vitro autoradiography showed that [18F]7a had high specific binding with mGluR1 in the rat brain. Biodistribution study using a dissection method and small-animal PET showed that [18F]7a had high uptake in the rat brain. The uptake of radioactivity in the cerebellum was reduced by unlabeled 7a and mGluR1-selective ligand JNJ-16259685 (2), indicating that [18F]7a had in vivo specific binding with mGluR1. Because of a low amount of radiolabeled metabolite present in the brain, [18F]7a may have a limiting potential for the in vivo imaging of mGluR1 by PET.