在用于强迫样行为的Sapap3基因敲除小鼠模型中，使用[C]ABP688和[F]FPEB正电子发射断层扫描法定量代谢型谷氨酸受体5的可用性。
Quantification of Metabotropic Glutamate Receptor 5 Availability With Both [C]ABP688 and [F]FPEB Positron Emission Tomography in the Sapap3 Knockout Mouse Model for Obsessive-Compulsive-like Behavior.
作者信息
Glorie Dorien, Verhaeghe Jeroen, Miranda Alan, De Lombaerde Stef, Stroobants Sigrid, Staelens Steven
机构信息
Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium.
Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium; Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
出版信息
Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Jun;7(6):607-615. doi: 10.1016/j.bpsc.2021.11.010. Epub 2021 Nov 29.
BACKGROUND
This study provides a first direct comparison between positron emission tomography radioligands targeting the allosteric site of the metabotropic glutamate receptor 5 (mGluR5): [C]ABP688 and [F]FPEB. A blocking paradigm was set up to substantiate the common binding site of both radioligands. Second, both radioligands were applied in Sapap3 knockout (KO) mice showing compulsive-like behavior characterized by a lower in vivo mGluR5 availability.
METHODS
First, wild-type mice (n = 7) received four position emission tomography/computed tomography scans: a [C]ABP688 scan, a [F]FPEB scan, and two blocking scans using cold FPEB and cold ABP688, respectively. A second experiment compared both radioligands in wild-type (n = 7) and KO (n = 10) mice. The simplified reference tissue model was used to calculate the nondisplaceable binding potential representing the in vivo availability of mGluR5 in the brain.
RESULTS
Using cold FPEB as a blocking compound for [C]ABP688 micro-positron emission tomography and vice versa, we observed averaged global reductions in mGluR5 availability of circa 98% for [C]ABP688 and 82%-96% for [F]FPEB. For KOs, the [C]ABP688 nondisplaceable binding potential was on average 25% lower compared with wild-type control mice (p < .0001-.001), while this was about 17% for [F]FPEB (p < .05).
CONCLUSIONS
The current findings substantiate a common binding site and suggest a strong relationship between mGluR5 availability levels measured with both radioligands. In Sapap3 KO mice, a reduced mGluR5 availability could therefore be demonstrated with both radioligands. With [C]ABP688, higher significance levels were achieved in more brain regions. These findings suggest [C]ABP688 as a preferable radiotracer to quantify mGluR5 availability, as exemplified here in a model for compulsive-like behavior.
背景
本研究首次对靶向代谢型谷氨酸受体5（mGluR5）变构位点的正电子发射断层扫描放射性配体进行了直接比较：[C]ABP688和[F]FPEB。建立了一种阻断范式以证实两种放射性配体的共同结合位点。其次，将两种放射性配体应用于表现出强迫样行为的Sapap3基因敲除（KO）小鼠，其特征是体内mGluR5的可用性较低。
方法
首先，野生型小鼠（n = 7）接受了四次正电子发射断层扫描/计算机断层扫描：一次[C]ABP688扫描、一次[F]FPEB扫描，以及分别使用冷FPEB和冷ABP688的两次阻断扫描。第二个实验比较了野生型（n = 7）和KO（n = 10）小鼠体内的两种放射性配体。使用简化参考组织模型来计算代表大脑中mGluR5体内可用性的不可置换结合潜力。
结果
使用冷FPEB作为[C]ABP688微正电子发射断层扫描的阻断化合物，反之亦然，我们观察到[C]ABP688的mGluR5可用性平均整体降低约98%，[F]FPEB降低82%-96%。对于基因敲除小鼠，[C]ABP688的不可置换结合潜力平均比野生型对照小鼠低25%（p <.0001-.001），而[F]FPEB约为17%（p <.05）。
结论
目前的研究结果证实了一个共同的结合位点，并表明用两种放射性配体测量的mGluR5可用性水平之间存在密切关系。因此，在Sapap3基因敲除小鼠中，可以用两种放射性配体证明mGluR5可用性降低。使用[C]ABP688时，在更多脑区获得了更高的显著性水平。这些发现表明，[C]ABP688是一种更适合量化mGluR5可用性的放射性示踪剂，如此处强迫样行为模型所示。
Zotero 插件