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Positron emission tomography (PET) imaging probes for GlyT1 are, consequently, expected to be useful for investigating the mechanism of such disease conditions and for measuring occupancy of GlyT1 inhibitors<jats:italic>in vivo<\/jats:italic>. The aim of this study was to assess the potential of 2-chloro<jats:italic>N<\/jats:italic>-[(<jats:italic>S<\/jats:italic>)-{(<jats:italic>S<\/jats:italic>)-1-[<jats:sup>11<\/jats:sup>\u2009C]methylpiperidin-2-yl} (phenyl)methyl] 3-trifluoromethyl-benzamide ([<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734) as a PET imaging agent for GlyT1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>[<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 was synthesized by<jats:italic>N<\/jats:italic>-[<jats:sup>11<\/jats:sup>\u2009C]methylation of SSR504734 via [<jats:sup>11<\/jats:sup>\u2009C]CH<jats:sub>3<\/jats:sub>OTf.<jats:italic>In vitro<\/jats:italic>brain distribution of [<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 was tested in whole-hemisphere autoradiography (ARG) on human brain slices. Initial PET studies were performed using a cynomolgus monkey at baseline and after pretreatment with 0.1 to 1.5\u2009mg\/kg of SSR504734. Then, PET studies using rhesus monkeys were performed with arterial blood sampling at baseline and after pretreatment with 1.5 to 4.5\u2009mg\/kg SSR504734. Distribution volumes (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>) were calculated with a two-tissue compartment model, and GlyT1 occupancy by SSR504734 was estimated using a Lassen plot approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>[<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 was successfully synthesized in moderate radiochemical yield and high specific radioactivity. In the ARG experiments, [<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 showed specific binding in the white matter and pons. In the initial PET experiments in a cynomolgus monkey, [<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 showed high brain uptake and consistent distribution with previously reported GlyT1 expression<jats:italic>in vivo<\/jats:italic>(thalamus, brainstem\u2009&gt;\u2009cerebellum\u2009&gt;\u2009cortical regions). However, the brain uptake increased after pretreatment with SSR504734. Further PET studies in rhesus monkeys showed a similar increase of brain uptake after pretreatment with SSR504734. However, the<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>of [<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 was found to decrease after pretreatment of SSR504734 in a dose-dependent manner. GlyT1 occupancy was calculated to be 45% and 73% at 1.5 and 4.5\u2009mg\/kg of SSR504734, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>[<jats:sup>11<\/jats:sup>\u2009C]<jats:italic>N<\/jats:italic>-methyl-SSR504734 is demonstrated to be a promising PET radioligand for GlyT1 in nonhuman primates. The present results warrant further PET studies in human subjects.<\/jats:p><\/jats:sec>","DOI":"10.1186\/2191-219x-2-37","type":"journal-article","created":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T10:23:29Z","timestamp":1341829409000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis and evaluation of 2-chloro N-[(S)-{(S)-1-[11\u2009C]methylpiperidin-2-yl} (phenyl)methyl]3-trifluoromethyl-benzamide ([11\u2009C]N-methyl-SSR504734) as a PET radioligand for glycine transporter 1"],"prefix":"10.1186","volume":"2","author":[{"given":"Takeshi","family":"Fuchigami","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Takano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Guly\u00e1s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhisheng","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sjoerd J","family":"Finnema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan D","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Nakao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Magata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Haratake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morio","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christer","family":"Halldin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,7,9]]},"reference":[{"key":"95_CR1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0031-6997(24)01382-6","volume":"50","author":"W Danysz","year":"1998","unstructured":"Danysz W, Parsons CG: Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications. 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