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ID: ALA2176994

Journal: Bioorg Med Chem Lett

Title: Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo.

Authors: Wang JQ, Zhang Z, Kuruppu D, Brownell AL.

Abstract: Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study group II mGluRs in vivo under physiologic and pathologic conditions. We synthesized a PET tracer, (S,S,S)-2-(2-carboxycyclopropyl)-2-(3-[(11)C]methoxyphenethyl) glycine dimethyl ester ([(11)C]CMGDE), as a prodrug for group II mGluRs, and studied its preliminary biological properties in Sprague-Dawley rats to visualize group II mGluRs. The microPET studies demonstrated that [(11)C]CMGDE readily penetrated into the brain and the radiotracer generated from [(11)C]CMGDE had fast reversible binding in the group II mGluRs rich regions including striatum, hippocampus and different cortical areas. Blocking studies with LY341495 showed 20-30% decrease of binding of the radiotracer generated from [(11)C]CMGDE in all brain areas with the highest decrease in the striatum 31.5±3.2%. The results show [(11)C]CMGDE is the first PET tracer that is brain penetrating and can be used to image group II mGluRs in vivo.

CiteXplore: 22318160

DOI: 10.1016/j.bmcl.2012.01.039