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- Title
Measuring the effects of ketamine on mGluR5 using [ 18 F]FPEB and PET.
- Authors
Holmes, Sophie E; Gallezot, Jean-Dominique; Davis, Margaret T; DellaGioia, Nicole; Matuskey, David; Nabulsi, Nabeel; Krystal, John H; Javitch, Jonathan A; DeLorenzo, Christine; Carson, Richard E; Esterlis, Irina
- Abstract
The metabotropic glutamate receptor 5 (mGluR5) is a promising treatment target for psychiatric disorders due to its modulatory effects on glutamate transmission. Using [11C]ABP688, we previously showed that the rapidly acting antidepressant ketamine decreases mGluR5 availability. The mGluR5 radioligand [18F]FPEB offers key advantages over [11C]ABP688; however, its suitability for drug challenge studies is unknown. We evaluated whether [18F]FPEB can be used to capture ketamine-induced effects on mGluR5. Seven healthy subjects participated in three [18F]FPEB scans: a baseline, a same-day post-ketamine, and a 24-h post-ketamine scan. The outcome measure was V T/ f P, obtained using a two-tissue compartment model and a metabolite-corrected arterial input function. Dissociative symptoms, heart rate and blood pressure increased following ketamine infusion. [18F]FPEB V T/ f P decreased by 9% across the cortex after ketamine infusion, with minimal difference between baseline and 24-h scans. Compared to our previous work using [11C]ABP688, the magnitude of the ketamine-induced change in mGluR5 was smaller using [18F]FPEB; however, effect sizes were similar for the same-day post-ketamine vs. baseline scan (Cohen's d = 0.75 for [18F]FPEB and 0.88 for [11C]ABP688). [18F]FPEB is therefore able to capture some of the effects of ketamine on mGluR5, but [11C]ABP688 appears to be more suitable in drug challenge paradigms designed to probe glutamate transmission.
- Publication
Journal of Cerebral Blood Flow & Metabolism, 2020, Vol 40, Issue 11, p2254
- ISSN
0271-678X
- Publication type
Article
- DOI
10.1177/0271678X19886316