title: Metabotropic Glutamate Receptor Type 5 (mGluR5) Cortical Abnormalities in Focal Cortical Dysplasia Identified In Vivo With [11C]ABP688 Positron-Emission Tomography (PET) Imaging.
abstract: Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses.
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
authors: Jonathan M
authors: JM
authors: DuBois
authors: Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University, Baltimore, MD 21287, USA.
authors: Olivier G
authors: OG
authors: Rousset
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.|Department of Pathology, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors: Marie-Christine
authors: MC
authors: Guiot
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
authors: Jeffery A
authors: JA
authors: Hall
authors: PET Unit, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.|Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, London SE1 7EH, UK.
authors: Andrew J
authors: AJ
authors: Reader
authors: PET Unit, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.|Bio-Imaging Group, PERFORM Centre, Concordia University, Montreal, Quebec, Canada H4B 1R6.
authors: Jean-Paul
authors: JP
authors: Soucy
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.|PET Unit, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.|Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada H4H 1R3.
authors: Pedro
authors: P
authors: Rosa-Neto
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
authors: Eliane
authors: E
authors: Kobayashi
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000000981:diagnostic imaging* / Q000473:pathology; D008875:Middle Aged; D010091:Oximes / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D055815:Young Adult
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; C578935:GRM5 protein, human; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5
keywords: [11C]ABP688; epilepsy; focal cortical dysplasia; metabotropic glutamate receptor type 5; positron-emission tomography