Sophie E Holmes, Jean-Dominique Gallezot, Margaret T Davis, Nicole DellaGioia, David Matuskey, Nabeel Nabulsi, John H Krystal, Jonathan A Javitch, Christine DeLorenzo, Richard E Carson, Irina Esterlis
{"title":"Measuring the effects of ketamine on mGluR5 using [<sup>18</sup>F]FPEB and PET.","authors":"Sophie E Holmes, Jean-Dominique Gallezot, Margaret T Davis, Nicole DellaGioia, David Matuskey, Nabeel Nabulsi, John H Krystal, Jonathan A Javitch, Christine DeLorenzo, Richard E Carson, Irina Esterlis","doi":"10.1177/0271678X19886316","DOIUrl":null,"url":null,"abstract":"<p><p>The metabotropic glutamate receptor 5 (mGluR5) is a promising treatment target for psychiatric disorders due to its modulatory effects on glutamate transmission. Using [<sup>11</sup>C]ABP688, we previously showed that the rapidly acting antidepressant ketamine decreases mGluR5 availability. The mGluR5 radioligand [<sup>18</sup>F]FPEB offers key advantages over [<sup>11</sup>C]ABP688; however, its suitability for drug challenge studies is unknown. We evaluated whether [<sup>18</sup>F]FPEB can be used to capture ketamine-induced effects on mGluR5. Seven healthy subjects participated in three [<sup>18</sup>F]FPEB scans: a baseline, a same-day post-ketamine, and a 24-h post-ketamine scan. The outcome measure was <i>V</i><sub>T</sub>/<i>f</i><sub>P</sub>, 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. [<sup>18</sup>F]FPEB <i>V</i><sub>T</sub>/<i>f</i><sub>P</sub> decreased by 9% across the cortex after ketamine infusion, with minimal difference between baseline and 24-h scans. Compared to our previous work using [<sup>11</sup>C]ABP688, the magnitude of the ketamine-induced change in mGluR5 was smaller using [<sup>18</sup>F]FPEB; however, effect sizes were similar for the same-day post-ketamine vs. baseline scan (Cohen's d = 0.75 for [<sup>18</sup>F]FPEB and 0.88 for [<sup>11</sup>C]ABP688). [<sup>18</sup>F]FPEB is therefore able to capture some of the effects of ketamine on mGluR5, but [<sup>11</sup>C]ABP688 appears to be more suitable in drug challenge paradigms designed to probe glutamate transmission.</p>","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X19886316","citationCount":"9","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cerebral Blood Flow & Metabolism","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/0271678X19886316","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/11/19 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 9
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 VT/fP, 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 VT/fP 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.