Quantification of Metabotropic Glutamate Receptor 5 Availability With Both [11C]ABP688 and [18F]FPEB Positron Emission Tomography in the Sapap3 Knockout Mouse Model for Obsessive-Compulsive–like Behavior

This study provides a first direct comparison between positron emission tomography (PET) radioligands targeting the allosteric site of the metabotropic glutamate receptor 5 (mGluR5): [11C]ABP688 and [18F]FPEB. A blocking paradigm was set up to substantiate the common binding site of both radioligands. Second, both radioligands were applied in Sapap3 knockouts showing compulsive-like behavior characterized by a lower in vivo mGluR5 availability. METHODS First, wildtype mice (n=7) received four μPET/CT scans: an [11C]ABP688 and [18F]FPEB scan, and two blocking scans using cold FPEB and cold ABP688, respectively. A second experiment compared both radioligands in wildtype (n=7) and Sapap3 knockout mice (n=10). The simplified reference tissue method was used to calculate the nondisplaceable binding potential (BPND) representing the in vivo availability of the mGluR5 in the brain. RESULTS Using cold FPEB as a blocking compound for [11C]ABP688 μPET and vice versa, we observed averaged global reductions in mGluR5 availability of circa 98% for [11C]ABP688 and 82%-96% for [18F]FPEB. For knockouts, the [11C]ABP688 BPND was on average 25% lower compared to wildtype controls (p