Abstract Details

Title Focal mGluR5 Abnormalities Identified in vivo in Mesial Temporal Lobe Epilepsy (MTLE) by [11C]ABP688 Positron Emission Tomography (PET)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S36 - Epilepsy/Clinical Neurophysiology (EEG) II (1:11 PM-1:22 PM)

Poster/Presentation
Number 002

Background mGluR5 upregulation has been identified in immunohistochemistry studies of hippocampi resected from mesial temporal lobe epilepsy (MTLE) patients with and without hippocampal sclerosis. Because of the small size of the tissue sample, it remains to be clarified whether these abnormalities are specific to the epileptogenic zone.

Objective To characterize whole brain in vivo metabotropic glutamate receptor type 5 (mGluR5) availability in MTLE patients using positron emission tomography (PET) imaging of [¹¹C]ABP688 (a radioligand specific for the allosteric site of mGluR5).

Design/Methods Thirty-one unilateral MTLE patients and 30 healthy controls underwent structural MRI and [¹¹C]ABP688 PET. Patients were classified as “normal volume” (NV) or “hippocampal atrophy” (HA) based on hippocampal volume asymmetry. We utilized a region-of-interest and a whole-brain voxel-wise approach to compare partial volume corrected [¹¹C]ABP688 non-displaceable binding potentials (BP_ND) between patient groups (i.e., NV and HA) and controls. In addition, we further compared asymmetry indices of [¹¹C]ABP688 BP_NDand [¹⁸F]fluorodeoxyglucose (FDG) uptake for 15 patients who also underwent [¹⁸F]FDG PET as part of their clinical investigation to determine differences in lateralization and localization.

Results Focal reductions in [¹¹C]ABP688 BP_NDas compared to controls were found in the ipsilateral hippocampal head and amygdala (p<0.001) in NV and HA patients. In HA patients, we observed more extensive reductions also involving the ipsilateral temporal neocortex (p=0.006). [¹¹C]ABP688 BP_NDwas able to accurately discriminate the epileptogenic zone, showing significant interhemispheric asymmetry only in the hippocampus while [¹⁸F]FDG uptake displayed more widespread hypometabolism.

Conclusions mGluR5 abnormalities assessed in vivo with [¹¹C]ABP688 PET indicate changes that are focal and localized to the epileptogenic region without widespread receptor change across the epileptic brain. Reduction of mGluR5 availability may reflect receptor internalization or conformational changes due to excess extracellular glutamate within the epileptogenic zone.

Authors/Disclosures
Jack Lam PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Pedro Rosa Neto, MD, PhD (McGIll University)	Dr. Rosa Neto has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk.
Eliane Kobayashi, MD, PhD (Montreal Neurological Institute, McGill University)	Dr. Kobayashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Knight pharmaceuticals. Dr. Kobayashi has received personal compensation in the range of $0-$499 for serving as a Consultant for Creative Research Designs. Dr. Kobayashi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmacuticals. Dr. Kobayashi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Paladin Laboratories. Dr. Kobayashi has received personal compensation in the range of $0-$499 for serving as a author with Medlink .

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