Dataset Information

Measuring the effects of ketamine on mGluR5 using [¹⁸F]FPEB and PET.

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.

SUBMITTER: Holmes SE

PROVIDER: S-EPMC7585925 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET.

Holmes Sophie E SE Gallezot Jean-Dominique JD Davis Margaret T MT DellaGioia Nicole N Matuskey David D Nabulsi Nabeel N Krystal John H JH Javitch Jonathan A JA DeLorenzo Christine C Carson Richard E RE Esterlis Irina I

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20191119 11

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 ...[more]

PMID: 31744389

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Dataset Information

Measuring the effects of ketamine on mGluR5 using [¹⁸F]FPEB and PET.

Publications

Measuring the effects of ketamine on mGluR5 using [<sup>18</sup>F]FPEB and PET.

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