Abstracts

Rationale: Metabotropic glutamate receptor subtype 1 (mGluR1) is a crucial target in the development of new medications to treat central nervous system disorders including epilepsy. Though some previous basic research suggested that the mGluR1/5 contributed to the formation of the epileptogenesis, their behavior was still unknown in the epilepsy patients. We have recently developed newly radiotracer, which was specific to the mGluR type1, N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl] -4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM), which made mGluR1 in vivo imaging possible using positron emission tomography (PET). We report the initial mGluR1 PET images of medial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS). Methods: Three mTLE patients with HS were included in this study. They completed three different PET studies preoperatively: (18)F-FDG (glucose metabolism), (11)C-flumazenil (FMZ: binding to the central benzodiazepine receptors) and (11)C-ITMM (binding to the mGluR1). Regions of interest (ROIs) were drawn manually on the each MRI. Template ROIS included hippocampus, amygdala, parahippocampal gyrus, lateral temporal cortex, and frontal cortex. Template ROIs were applied to each subject's PET image and mean voxel values were extracted for each ROI. Values of ipsilateralside were compared to the contralateral side. Results: (11)C-ITMM PET images showed that mGluR1 binding decreased in both sclerotic hippocampus and amygdala (78% of contralateral binding, 82%), but they unchanged in the lateral temporal and frontal cortex. (11)C-FMZ PET images revealed binding to the central benzodiazepine receptors decreased at hippocampus and amygdala (61%, 71 %), similar to the (11)C-ITMM PET study. (18)F-FDG PET showed glucose metabolism decreased in amygdala, hippocampus, parahippocampal gyrus and lateral temporal cortex (78%, 90%, 85% and 90%). Conclusions: We report the initial mGluR1 PET images of mTLE patients. Binding to the mGluR1 decreased at sclerotic hippocampus and amygdala, similar to the (11)C-FMZ PET study. These data suggested mGluR1 receptor decreased at epileptic foci because of the neuronal loss. (11)C-ITMM PET has potential to diagnose and visualize epileptic focus. Furthermore, (11)C-ITMM PET might be useful clinical imaging tool to clarify the mGluR1 contribution to the epilepsy. Funding: This study was supported by Research Grant of The Japan Epilepsy Research Foundation.