@article{oai:repo.qst.go.jp:00046746,
 author = {Kawamura, Kazunori and Yamasaki, Tomoteru and Kumata, Katsushi and Furutsuka, Kenji and Takei, Makoto and Wakizaka, Hidekatsu and Fujinaga, Masayuki and Kaori, Kariya and Yui, Joji and Hatori, Akiko and Xie, Lin and Shimoda, Yoko and Hashimoto, Hiroki and Hayashi, Kazutaka and Zhang, Ming-Rong and 河村 和紀 and 山崎 友照 and 熊田 勝志 and 古塚 賢士 and 武井 誠 and 脇坂 秀克 and 藤永 雅之 and 由井 譲二 and 羽鳥 晶子 and 謝 琳 and 下田 陽子 and 橋本 裕輝 and 林 和孝 and 張 明栄},
 issue = {1},
 journal = {Nuclear Medicine and Biology},
 month = {Sep},
 note = {Introduction: [11C]ABP688 is a promising positron emission tomography (PET) ligand for imaging of
metabotropic glutamate receptor subtype 5 (mGlu5 receptor). Of the two geometric isomers of ABP688, (E)-
ABP688 has a greater affinity towards mGlu5 receptors than (Z)-ABP688. Therefore, a high ratio of E-isomer is
required when using [11C]ABP688 as a PET probe for imaging and quantification of mGlu5 receptors. The aim
of this study was to evaluate the effect (Z)-[11C]ABP688 on the synthesis of [11C]ABP688 to be used for binding
(E)-[11C]ABP688 in the brain.
Methods: We synthesized and separated (E)- and (Z)-[11C]ABP688 by purification using an improved
preparative high-performance liquid chromatography (HPLC) method equipped with a COSMOSIL Cholester
column. We performed an in vitro binding assay in rat brain homogenates and PET studies of the rat brains
using (E)- and (Z)-[11C]ABP688.
Results: (E)- and (Z)-[11C]ABP688 were successfully obtained with suitable radioactivity for application. In the
in vitro assay, the Kd value of (E)-[11C]ABP688 (5.7 nmol/L) was higher than that of (Z)-[11C]ABP688 (140
nmol/L). In the PET study of the rat brain, high radioactivity after injection of (E)-[11C]ABP688 was observed in
regions rich in mGlu5 receptors such as the striatum and hippocampus. In contrast, after injection of (Z)-[11C]
ABP688, radioactivity did not accumulate in the brain. Furthermore, BPND in the striatum and hippocampus
was highly correlated (R2=0.99) with the percentage of (E)-[11C]ABP688 of the total radioactivity of (E)- and
(Z)-[11C]ABP688 in the injection.
Conclusion: We demonstrated that including (Z)-[11C]ABP688 in the [11C]ABP688 injection can decrease BPND
in regions rich in mGlu5 receptors. Routine production of (E)-[11C]ABP688 will be helpful for imaging and
quantification of mGlu5 receptors in clinical studies.},
 pages = {17--23},
 title = {Binding potential of (E)-[11C]ABP688 to metabotropic glutamate receptor subtype 5 is decreased by the inclusion of its 11C-labelled Z-isomer},
 volume = {41},
 year = {2013}
}