Title: Synthesis, evaluation, and radiolabeling of new potent positive allosteric modulators of the metabotropic glutamate receptor 2 as potential tracers for positron emission tomography imaging
Authors: Andrés, José-Ignacio ×
Alcázar, Jesús
Cid, José María
De Angelis, Meri
Iturrino, Laura
Langlois, Xavier
Lavreysen, Hilde
Trabanco, Andrés A
Celen, Sofie
Bormans, Guy #
Issue Date: Oct-2012
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:55 issue:20 pages:8685-8699
Article number: 10.1021/jm300912k
Abstract: The synthesis and in vitro and in vivo evaluation of a new series of 7-(phenylpiperidinyl)-1,2,4-triazolo[4,3-a]pyridines, which were conveniently radiolabeled with carbon-11, as potential positron emission tomography (PET) radiotracers for in vivo imaging of the allosteric binding site of the metabotropic glutamate (mGlu) receptor subtype 2 are described. The synthesized compounds proved to be potent and selective positive allosteric modulators (PAMs) of the mGlu receptor 2 (mGluR2) in a [³⁵S]GTPγS binding assay and were able to displace an mGluR2 PAM radioligand, which we had previously developed, with IC₅₀ values in the low nanomolar range. The most promising candidates were radiolabeled and subjected to biodistribution studies and radiometabolite analysis in rats. Preliminary small-animal PET (μPET) studies in rats indicated that [¹¹C]20f binds specifically and reversibly to an mGluR2 allosteric site, strongly suggesting that it is a promising candidate for PET imaging of mGluR2 in the brain.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Radiopharmacy
× corresponding author
# (joint) last author

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