量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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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.
Binding potential of (E)-[11C]ABP688 to metabotropic glutamate receptor subtype 5 is decreased by the inclusion of its 11C-labelled Z-isomer
