In Vivo Imaging of mGluR5 Changes during Epileptogenesis Using [11C]ABP688 PET in Pilocarpine-Induced Epilepsy Rat Model

Introduction: Metabotropic glutamate receptor 5 (mGluR5) that regulates glutamatergic neurotransmission contributes to pathophysiology of epilepsy. In this study, we monitored the changes of mGluR5 in vivo using [C-11]ABP688 PET during the epileptogenesis in a pilocarpine-induced epilepsy rat model. Methods: In vivo mGluR5 images were acquired using [C-11]ABP688 microPET/CT in pilocarpine-induced chronic epilepsy rat models and controls. We also acquired microPET/CT at acute, subacute as well as chronic periods after status epilepticus. Non-displaceable binding potential (BPND) of [C-11]ABP688 was calculated using simplified reference tissue model in a voxel-based manner. mGluR5 BPND of the rat brains of epilepsy models and controls were compared. Results: Status epilepticus developed after pilocarpine administration and was followed by recurrent spontaneous seizures for more than 3 weeks. In chronic epilepsy rat model, BPND in hippocampus and amygdala was reduced on a voxel-based analysis. Temporal changes of mGluR5 BPND was also found. In acute period after status epilepticus, mGluR5 BPND was reduced in the whole brain. BPND of caudate-putamen was restored in subacute period, while BPND of the rest of the brain was still lower. In chronic period, global BPND was normalized except in hippocampus and amygdala. Conclusions: In vivo imaging of mGluR5 using [C-11]ABP688 microPET/CT could successfully reveal the regional changes of mGluR5 binding potential of the rat brain in a pilocarpine-induced epilepsy model. The temporal and spatial changes in mGluR5 availability suggest [C-11]ABP688 PET imaging in epilepsy provide abnormal glutamatergic network during epileptogenesis.