Activated N-methyl-D-aspartate receptor ion channels detected in focal epilepsy with [ F]GE-179 positron emission tomography.

Objective: Imaging activated glutamate N-methyl-D-aspartate receptor ion channels (NMDAR-ICs) using positron emission tomography (PET) has proved challenging due to low brain uptake, poor affinity and selectivity, and high metabolism and dissociation rates of candidate radioligands. The radioligand [ F]GE-179 is a known use-dependent marker of NMDAR-ICs. We studied whether interictal [ F]GE-179 PET would detect foci of abnormal NMDAR-IC activation in patients with refractory focal epilepsy.

NMDA receptor ion channel activation detected in vivo with [F]GE-179 PET after electrical stimulation of rat hippocampus.

The positron emission tomography (PET) tracer [F]GE-179 binds to the phencyclidine (PCP) site in the open -methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [F]GE-179 uptake by active NMDAR-ICs and that this can be blocked by the PCP antagonist S-ketamine, 15 rats had an electrode unilaterally implanted in their ventral hippocampus. Seven rats had no stimulation, five received pulsed 400 µA supra-threshold 60 Hz stimulation alone, and three received intravenous S-ketamine injection prior to stimulation.

Activation of NMDA receptor ion channels by deep brain stimulation in the pig visualised with [F]GE-179 PET.

Background: No PET radioligand has yet demonstrated the capacity to map glutamate N-methyl-d-aspartate receptor ion channel (NMDAR-IC) function. [F]GE-179 binds to the phencyclidine (PCP) site in open NMDAR-ICs and potentially provides a use-dependent PET biomarker of these ion channels.

Objective: To show [F]GE-179 PET can detect increased NMDAR-IC activation during electrical deep brain stimulation (DBS) of pig hippocampus.