Journal Article N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase.

Shimoda, Yoko  ,  Fujinaga, Masayuki  ,  Hatori, Akiko  ,  Yui, Joji  ,  Zhang, Yiding  ,  Nengaki, Nobuki  ,  Kurihara, Yusuke  ,  Yamasaki, Tomoteru  ,  Xie, Lin  ,  Kumata, Katsushi  ,  Ishii, Hideki  ,  Ming-Rong, Zhang

24 ( 4 )  , pp.627 - 634 , 2016-02 , Elsevier Science
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-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide ([(11)C]DFMC, [(11)C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1nM) for FAAH. [(11)C]1 was synthesized by C-(11)C coupling reaction of arylboronic ester 2 with [(11)C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [(11)C]1 was obtained with a radiochemical yield of 20±10% (based on [(11)C]CO2, decay-corrected, n=5) and specific activity of 48-166GBq/μmol. After the injection of [(11)C]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 [(11)C]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 30min after the radioligand injection. The present results indicate that [(11)C]1 is a promising PET ligand for imaging of FAAH in living brain.

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