title: Development of [(18)F]-PSS223 as a PET tracer for imaging of metabotropic glutamate receptor subtype 5 (mGluR5).
abstract: Involvement of metabotropic glutamate receptor subtype 5 (mGluR5) in physiological and pathophysiological processes in the brain has been demonstrated, and hence mGluR5 has emerged as an important drug target. [(11)C]-ABP688 is clinically the most successful mGluR5 positron  emission tomography (PET) tracer to date and it allows visualization and quantification of mGluR5. Due to the short half-life of carbon-11, clinical use of [(11)C]-ABP688 is limited to facilities with an on-site cyclotron and a fluorine-18 (half-life 110 min) analogue would be more  practical. Based on the [(11)C]-ABP688 structural motif, a novel derivative [(18)F]-PSS223 was prepared and evaluated as a PET tracer for imaging of mGluR5 in vitro and in vivo. Our results show favourable in vitro binding properties; however rapid defluorination  of [(18)F]-PSS223 does not allow visualization of mGluR5 in the rat brain.
authors.affiliation: Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland.
authors.forename: Selena Milicevic
authors.initials: SM
authors.lastname: Sephton
authors.forename: Patrick
authors.initials: P
authors.lastname: Dennler
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Leutwiler
authors.forename: Linjing
authors.initials: L
authors.lastname: Mu
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Krämer
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D005462:Fluorine Radioisotopes; D010091:Oximes / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D005462:Fluorine Radioisotopes; C578937:Grm5 protein, rat; D010091:Oximes; C573116:PSS223; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate