1. Development of [18F]-PSS223 as a PET Tracer for Imaging of Metabotropic Glutamate Receptor Subtype 5 (mGluR5)
- Author
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Selena Milicevic Sephton, Patrick Dennler, Simon M. Ametamey, Stefanie D. Krämer, Linjing Mu, Roger Schibli, Dominique S. Leutwiler, University of Zurich, and Ametamey, Simon M
- Subjects
Fluorine Radioisotopes ,Pyridines ,Receptor, Metabotropic Glutamate 5 ,animal diseases ,Drug Evaluation, Preclinical ,[18 f]-pss223 ,610 Medicine & health ,1600 General Chemistry ,Pet imaging ,Receptors, Metabotropic Glutamate ,[11 c]-abp688 ,Rats, Sprague-Dawley ,In vivo ,Mglur5 ,Oximes ,mental disorders ,medicine ,Animals ,Pet tracer ,Structural motif ,QD1-999 ,medicine.diagnostic_test ,Metabotropic glutamate receptor 5 ,Chemistry ,[18 f]-fdegpeco ,General Medicine ,General Chemistry ,10181 Clinic for Nuclear Medicine ,Rat brain ,In vitro ,Rats ,nervous system ,Positron emission tomography ,Metabotropic glutamate receptor ,Positron-Emission Tomography ,Biophysics ,Radiopharmaceuticals - 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. [11C]-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 [11C]-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 [11C]-ABP688 structural motif, a novel derivative [18F]-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 [18F]-PSS223 does not allow visualization of mGluR5 in the rat brain.
- Published
- 2012