Binding potential of (E)-[C-11]ABP688 to metabotropic glutamate receptor subtype 5 is decreased by the inclusion of its C-11-labelled Z-isomer

作者：Kawamura Kazunori^*; Yamasaki Tomoteru; Kumata Katsushi; Furutsuka Kenji; Takei Makoto; Wakizaka Hidekatsu; Fujinaga Masayuki; Kariya Kaori; Yui Joji; Hatori Akiko; Xie Lin; Shimoda Yoko; Hashimoto Hiroki; Hayashi Kazutaka; Zhang Ming Rong

来源：Nuclear Medicine and Biology, 2014, 41(1): 17-23.

DOI：10.1016/j.nucmedbio.2013.09.008

• C-11
• (E)-ABP688
• (Z)-ABP688
• Metabotropic glutamate receptor subtype 5
• Positron emission tomography

Introduction: [C-11]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 [C-11]ABP688 as a PET probe for imaging and quantification of mGlu5 receptors. The aim of this study was to evaluate the effect (Z)-[C-11]ABP688 on the synthesis of [C-11]ABP688 to be used for binding (E)-[C-11]ABP688 in the brain.
Methods: We synthesized and separated (E)- and (Z)-[C-11]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)-[C-11]ABP688.
Results: (E)- and (Z)-[C-11]ABP688 were successfully obtained with suitable radioactivity for application. In the in vitro assay, the K-d value of (E)-[C-11]ABP688 (5.7 nmol/L) was higher than that of (Z)-[C-11]ABP688 (140 nmol/L). In the PET study of the rat brain, high radioactivity after injection of (E)-[C-11]ABP688 was observed in regions rich in mGlu5 receptors such as the striatum and hippocampus. In contrast, after injection of (Z)-[C-11] ABP688, radioactivity did not accumulate in the brain. Furthermore, BPND in the striatum and hippocampus was highly correlated (R-2 = 0.99) with the percentage of (E)-[C-11]ABP688 of the total radioactivity of (E)- and (Z)-[C-11]ABP688 in the injection.
Conclusion: We demonstrated that including (Z)-[C-11]ABP688 in the [C-11]ABP688 injection can decrease BPND in regions rich in mGlu5 receptors. Routine production of (E)-[C-11]ABP688 will be helpful for imaging and quantification of mGlu5 receptors in clinical studies.

• 出版日期2014-1