Development of [18F]-PSS223 as a PET Tracer for Imaging of Metabotropic Glutamate Receptor Subtype 5 (mGluR5)
Selena Milicevic Sephton,
Patrick Dennler,
Dominique S. Leutwiler,
Linjing Mu,
Roger Schibli,
Stefanie D. Krämer,
Simon M. Ametamey
Affiliations
Selena Milicevic Sephton
SCS-Metrohm Foundation Award for best oral presentation, Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland
Patrick Dennler
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland
Dominique S. Leutwiler
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland
Linjing Mu
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland
Roger Schibli
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland
Stefanie D. Krämer
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland
Simon M. Ametamey
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences ETH-Hönggerberg, Wolfgang-Pauli Strasse 10, CH-8093 Zürich, Switzerland. [email protected]
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.
