Dataset Information

NMDA receptor ion channel activation detected in vivo with [¹⁸F]GE-179 PET after electrical stimulation of rat hippocampus.

ABSTRACT: The positron emission tomography (PET) tracer [¹⁸F]GE-179 binds to the phencyclidine (PCP) site in the open N-methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [¹⁸F]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. Six other rats were not implanted. Each rat had a 90 min [¹⁸F]GE-179 PET scan. Stimulated rats had simultaneous depth-EEG recordings of induced seizure activity. [¹⁸F]GE-179 uptake (volume of distribution, V_T) was compared between hemispheres and between groups. Electrical stimulation induced a significant increase in [¹⁸F]GE-179 uptake at the electrode site compared to the contralateral hippocampus (mean 22% increase in V_T, p = 0.0014) and to non-stimulated comparator groups. Rats injected with S-ketamine prior to stimulation maintained non-stimulated levels of [¹⁸F]GE-179 uptake during stimulation. In conclusion, PET visualisation of focal [¹⁸F]GE-179 uptake during electrically activated NMDAR-ICs and the demonstration of specificity for PCP sites by blockade with S-ketamine support the in vivo utility of [¹⁸F]GE-179 PET as a use-dependent marker of NMDAR-IC activation.

SUBMITTER: Vibholm AK

PROVIDER: S-EPMC8142139 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NMDA receptor ion channel activation detected in vivo with [18F]GE-179 PET after electrical stimulation of rat hippocampus.

Vibholm Ali K AK Landau Anne M AM Møller Arne A Jacobsen Jan J Vang Kim K Munk Ole L OL Orlowski Dariusz D Sørensen Jens Ch JC Brooks David J DJ

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20200922 6

The positron emission tomography (PET) tracer [18F]GE-179 binds to the phencyclidine (PCP) site in the open N-methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [18F]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 ...[more]

PMID: 32960687

Similar Datasets

Project description:PurposeWhile the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using 18F-fluorodeoxyglucose (18F-FDG) or tracers targeting the translocator protein (TSPO). To evaluate 18F-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared 18F-GE-180 uptake with that of 18F-FDG and DCE-MRI measures of inflammation.MethodsEight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with 18F-GE-180 and 18F-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUVmax). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient Ktrans using Pearson correlation (r).ResultsPET/CT imaging with 18F-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). 18F-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09-0.31). 18F-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUVmax vs. Ktrans: r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints).ConclusionsThe correlations between DCE-MRI parameters and 18F-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer 18F-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA.

Dataset Information

NMDA receptor ion channel activation detected in vivo with [¹⁸F]GE-179 PET after electrical stimulation of rat hippocampus.

Publications

NMDA receptor ion channel activation detected in vivo with [<sup>18</sup>F]GE-179 PET after electrical stimulation of rat hippocampus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets