@article{oai:repo.qst.go.jp:00047071,
 author = {Endo, Tadashi and Saijo, Takeaki and Haneda, Eisuke and Maeda, Jun and Tokunaga, Masaki and Zhang, Ming-Rong and Kannami, Ayako and Asai, Hidetoshi and Suzuki, Masayuki and Suhara, Tetsuya and Higuchi, Makoto and 遠藤 忠 and 西條 武明 and 前田 純 and 徳永 正希 and 張 明栄 and 須原 哲也 and 樋口 真人},
 issue = {2},
 journal = {The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)},
 month = {Oct},
 note = {Central substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets in the development of drugs against diverse conditions including emesis, overactive bladder and depression. Here, we applied small animal positron emission tomography (PET) and a radioligand for NK-1 receptors, [18F]FE-SPA-RQ, for measuring occupancies of these receptors by a selective antagonist, aprepitant, in order to examined the validity of this in vivo imaging system for preclinical characterization of candidate agents acting on NK-1 receptors, and as a tool for predicting optimal doses in humans. PET in gerbils depicted high uptake in the striatum and dose-dependent displacement with increasing dose of aprepitant. Occupancies increased as a function of aprepitant plasma concentrations according to a one-site competition model, in good agreement with reported occupancy-concentration relationships in clinical studies after correction for species differences in plasma protein-unbound aprepitant fractions. These occupancy data were further supported by ex vivo autoradiography of brain samples from aprepitant-treated gerbils. In a pilot study of a marmoset, we obtained more accurate determinations of NK-1 receptor occupancy, less affected by spillover of signals from extracranial tissues than in gerbil experiments. These findings support the utility of small animals and quantitative PET in the development of drugs targeting NK-1 receptors.},
 pages = {1--10},
 title = {Quantification of central substance P receptor occupancy by aprepitant using small animal positron emission tomography.},
 volume = {18},
 year = {2014}
}