Several studies showed that [11C]ABP688 binding is altered following drug-induced\nperturbation of glutamate levels in brains of humans, non-human primates and rats. We evaluated\nwhether the fluorinated derivative [18F]PSS232 can be used to assess metabotropic glutamate receptor\n5 (mGluR5) availability in rats after pharmacological challenge with ketamine, known to increase\nglutamate, or ceftriaxone, known to decrease glutamate. In vitro autoradiography was performed on\nrat brain slices with [18F]PSS232 to prove direct competition of the drugs for mGluR5. One group\nof rats were challenged with a bolus injection of either vehicle, racemic ketamine, S-ketamine or\nceftriaxone followed by positron emission tomography PET imaging with [18F]PSS232. The other\ngroup received an infusion of the drugs during the PET scan. Distribution volume ratios (DVRs) were\ncalculated using a reference tissue model. In vitro autoradiography showed no direct competition of\nthe drugs with [18F]PSS232 for the allosteric binding site of mGluR5. DVRs of [18F]PSS232 binding\nin vivo did not change in any brain region neither after bolus injection nor after infusion. We conclude\nthat [18F]PSS232 has utility for measuring mGluR5 density or occupancy of the allosteric site in vivo,\nbut it cannot be used to measure in vivo fluctuations of glutamate levels in the rat brain.
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