Abstract

Objective

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 [11C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site.

Methods

Thirty‐one unilateral MTLE patients and 30 healthy controls underwent [11C]ABP688 PET. We compared partial volume corrected [11C]ABP688 non‐displaceable binding potentials (BPND) between groups using region‐of‐interest and whole‐brain voxel‐wise analyses. [18F]fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [11C]ABP688 BPND and [18F]FDG uptake to compare lateralization and localization differences.

Results

[11C]ABP688 BPND 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). [11C]ABP688 BPND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [18F]FDG uptake, which showed more widespread hypometabolism. Amongst 23/25 operated patients with > 1 year follow‐up, 13 were seizure‐free (Engel Ia), and showed significantly lower [11C]ABP688 BPND in the ipsilateral entorhinal cortex.

Interpretation

[11C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [18F]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.

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