Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Translational Neuroimaging Laboratory, McGill University, Montreal, Quebec, Canada.
Ann Neurol. 2019 Feb;85(2):218-228. doi: 10.1002/ana.25404. Epub 2019 Jan 20.
Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [ C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site.
Thirty-one unilateral MTLE patients and 30 healthy controls underwent [ C]ABP688 PET. We compared partial volume corrected [ C]ABP688 nondisplaceable binding potentials (BP ) between groups using region-of-interest and whole-brain voxelwise analyses. [ F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [ C]ABP688 BP and [ F]FDG uptake to compare lateralization and localization differences.
[ C]ABP688 BP was focally reduced in the epileptogenic hippocampal head and amygdala (p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex (p = 0.006). [ C]ABP688 BP showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [ F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [ C]ABP688 BP in the ipsilateral entorhinal cortex.
[ C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [ F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1-11 ANN NEUROL 2019;85:218-228.
患有内侧颞叶癫痫（MTLE）的患者的手术标本显示代谢型谷氨酸受体 5（mGluR5）的组织浓度异常。为了明确这些异常是否仅存在于致痫区（EZ），我们使用正电子发射断层扫描（PET）和[C]ABP688 对 MTLE 患者的全脑 mGluR5 可用性进行了特征描述，[C]ABP688 是一种特异性结合 mGluR5 变构位点的放射性配体。
31 例单侧 MTLE 患者和 30 名健康对照者接受了[C]ABP688 PET。我们使用感兴趣区域和全脑体素分析比较了两组之间部分容积校正的[C]ABP688 不可置换结合势（BP）。15 例患者进行了[F]氟脱氧葡萄糖（FDG）PET 检查，我们计算了[C]ABP688 BP 和[F]FDG 摄取的不对称指数，以比较侧化和定位差异。
[C]ABP688 BP 在致痫性海马头部和杏仁核中局灶性降低（p <0.001）。伴有海马萎缩的患者显示出更广泛的异常，包括同侧颞叶新皮质（p = 0.006）。与[F]FDG 摄取相比，[C]ABP688 BP 的半球间差异更大，并且更准确地区分了致痫结构，后者显示出更广泛的低代谢。在 25 例接受手术治疗且随访时间超过 1 年的患者中，23 例患者无癫痫发作（Engel Ia），且同侧内嗅皮质的[C]ABP688 BP 显著降低。
与[F]FDG PET 相比，[C]ABP688 PET 提供了一种用于 MTLE EZ 的局灶性生物标志物，具有更高的空间准确性。EZ 中 mGluR5 可用性的局灶性降低可能反映了受体内化或对细胞外谷氨酸过度反应的构象变化，支持 mGluR5 作为人类 MTLE 治疗靶点的潜在作用。
Zotero 插件