Kim Vang Hansen

Activation of NMDA receptor ion channels by deep brain stimulation in the pig visualised with [18F]GE-179 PET

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BACKGROUND: No PET radioligand has yet demonstrated the capacity to map glutamate N-methyl-d-aspartate receptor ion channel (NMDAR-IC) function. [18F]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 [18F]GE-179 PET can detect increased NMDAR-IC activation during electrical deep brain stimulation (DBS) of pig hippocampus.

METHODS: Six minipigs had an electrode implanted into their right hippocampus. They then had a baseline [18F]GE-179 PET scan with DBS turned off followed by a second scan with DBS turned on. Brain [18F]GE-179 uptake at baseline and then during DBS was measured with PET. Cerebral blood flow (CBF) was measured with [15O]H2O PET at baseline and during DBS and parametric CBF images were generated to evaluate DBS induced CBF changes. Functional effects of injecting the PCP blocker MK-801 were also evaluated. Electrode positions were later histologically verified.

RESULTS: DBS induced a 47.75% global increase in brain [18F]GE-179 uptake (p = 0.048) compared to baseline. Global CBF was unchanged by hippocampal DBS. [18F]GE-179 PET detected a 5% higher uptake in the implanted compared with the non-implanted temporo-parietal cortex at baseline (p = 0.012) and during stimulation (p = 0.022). Administration of MK-801 before DBS failed to block [18F]GE-179 uptake during stimulation.

CONCLUSION: PET detected an increase in global brain [18F]GE-179 uptake during unilateral hippocampal DBS while CBF remained unchanged. These findings support that [18F]GE-179 PET provides a use-dependent marker of abnormal NMDAR-IC activation.

Original languageEnglish
JournalBrain Stimulation
Volume13
Issue4
Pages (from-to)1071-1078
Number of pages8
ISSN1935-861X
DOIs
Publication statusPublished - Apr 2020

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