N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase |
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| Institution: | 1. Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan;2. SHI Accelerator Service Co. Ltd, 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan;1. Electronic Technology Area, Instituto Nacional de Técnica Aeroespacial, 28850 Torrejón de Ardoz, Spain;2. Department of Computer Engineering, Space Research Group, Universidad de Alcalá, 28805 Alcalá de Henares, Spain;1. Faculty of Information Technology, Macau University of Science and Technology, Macau;2. Space Science Institute, Macau University of Science and Technology, Macau;3. INAF, Astronomical Observatory of Torino, Strada Osservatorio 20, 10025 Pino, Torinese, Italy;4. IMCCE, Observatoire de Paris, 77 Av. Denfert Rochereau, 75014 Paris, France;5. Institute of Astronomy, National Central University, Taiwan;1. Department of Mathematics, Motilal Nehru National Institute of Technology, Allahabad – 211004, Uttar Pradesh, India;2. Department of Mathematics, National Institute of Technology, Raipur-492010, Chhattisgarh, India;1. Faculty of Mathematics and Computer Science, Adam Mickiewicz University, Umultowska 87, 61-614 Poznań, Poland;2. Bergische Universität Wuppertal, FB C – Mathematik, Gaußstraße 20, 42119 Wuppertal, Germany |
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| Abstract: | To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-4-(2-fluoro-4-11C]methylphenyl)thiazol-2-yl]-1-carboxamide (11C]DFMC, 11C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1 nM) for FAAH. 11C]1 was synthesized by C–11C coupling reaction of arylboronic ester 2 with 11C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, 11C]1 was obtained with a radiochemical yield of 20 ± 10% (based on 11C]CO2, decay-corrected, n = 5) and specific activity of 48–166 GBq/μmol. After the injection of 11C]1 in mice, high uptake of radioactivity (>2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for 11C]1 revealed high uptakes in the cerebellar nucleus (SUV = 2.4) and frontal cortex (SUV = 2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30 min after the radioligand injection. The present results indicate that 11C]1 is a promising PET ligand for imaging of FAAH in living brain. |
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| Keywords: | PET Fatty acid amide hydrolase Irreversible specific binding |
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