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Pharmaceuticals 2018, 11(3), 83; https://doi.org/10.3390/ph11030083

Ketamine and Ceftriaxone-Induced Alterations in Glutamate Levels Do Not Impact the Specific Binding of Metabotropic Glutamate Receptor Subtype 5 Radioligand [18F]PSS232 in the Rat Brain

1
Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, 8093 Zurich, Switzerland
2
Department of Nuclear Medicine, University Hospital Zurich, 8091 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Received: 24 July 2018 / Revised: 23 August 2018 / Accepted: 25 August 2018 / Published: 29 August 2018
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Abstract

Several studies showed that [11C]ABP688 binding is altered following drug-induced perturbation of glutamate levels in brains of humans, non-human primates and rats. We evaluated whether the fluorinated derivative [18F]PSS232 can be used to assess metabotropic glutamate receptor 5 (mGluR5) availability in rats after pharmacological challenge with ketamine, known to increase glutamate, or ceftriaxone, known to decrease glutamate. In vitro autoradiography was performed on rat brain slices with [18F]PSS232 to prove direct competition of the drugs for mGluR5. One group of rats were challenged with a bolus injection of either vehicle, racemic ketamine, S-ketamine or ceftriaxone followed by positron emission tomography PET imaging with [18F]PSS232. The other group received an infusion of the drugs during the PET scan. Distribution volume ratios (DVRs) were calculated using a reference tissue model. In vitro autoradiography showed no direct competition of the drugs with [18F]PSS232 for the allosteric binding site of mGluR5. DVRs of [18F]PSS232 binding in vivo did not change in any brain region neither after bolus injection nor after infusion. We conclude that [18F]PSS232 has utility for measuring mGluR5 density or occupancy of the allosteric site in vivo, but it cannot be used to measure in vivo fluctuations of glutamate levels in the rat brain. View Full-Text
Keywords: glutamate; metabotropic glutamate receptor subtype 5; [18F]PSS232; ketamine; ceftriaxone; positron emission tomography; allosteric modulator; MMPEP; ABP688 glutamate; metabotropic glutamate receptor subtype 5; [18F]PSS232; ketamine; ceftriaxone; positron emission tomography; allosteric modulator; MMPEP; ABP688
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Müller Herde, A.; Boss, S.D.; He, Y.; Schibli, R.; Mu, L.; Ametamey, S.M. Ketamine and Ceftriaxone-Induced Alterations in Glutamate Levels Do Not Impact the Specific Binding of Metabotropic Glutamate Receptor Subtype 5 Radioligand [18F]PSS232 in the Rat Brain. Pharmaceuticals 2018, 11, 83.

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