PET imaging with [11C]ITDM, a selective radioligand for metabotropic glutamate receptor subtype 1 (mGluR1), in pilocarpine-induced epileptic rat brain

Aim: Epilepsy is known as one of neurological diseases characterized by epileptic seizures induced via overstimulation of glutamatergic neurons. The metabotropic glutamate receptors (mGluRs) moderate in excitatory neurotransmission upon the central nerves system (CNS). Among mGluRs, mGluR1 is known as a trigger of neurotoxic cascades. In this study, we aimed to in vivo monitor regional changes of mGluR1 in pilocarpine-induced status epilepticus (PISE) model rat brains via longitude PET assessments.Methods: PISE model rats were induced by repeated pilocarpine hydrochloride treatments (10 mg/kg) after administration with lithium chloride (127 mg/kg). PET assessments with N-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]-methylbezamide ([11C]ITDM), a selective radioligand for mGluR1, were scheduled in acute (1 day), subacute (1 week), and chronic (3 weeks) periods after status epilepticus (SE). Acquired PET data were analysed with reference tissue models by PMOD software. To validate results of PET assessments, in vitro autoradiography with [11C]ITDM was performed using PISE rat brain sections prepared in same experimental period used in PET experiments.Results: In PET assessment with [11C]ITDM, binding potential (BPND) in the 1-3 cerebellar lobes significantly decreased (P < 0.001) in acute period (BPND = 3.2), subsequently recovering to normal level over subacute period (BPND = 4.6). Additionally, thalamic and hippocampal BPNDs showed gradual declines with time after SE over chronic period. However, in vitro autoradiography showed no change of specifically bindings of [11C]ITDM in the cerebellum in acute period, whereas bindings of [11C]ITDM in the thalamus and hippocampus indicated a tendency of decrease with time after SE. Conclusion: Our study indicates that gradual declines of mGluR1 expressions in the thalamus and hippocampus of PISE model rat brain via longitude PET imaging. In vivo monitoring of mGluR1 using PET with [11C]ITDM may enable to further understand mechanism involved in dysfunction of CNS.EANM 2016 Annual Congres