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.
(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.
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.