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.