title: Preclinical Evaluation and Quantification of 18F-FPEB as a Radioligand for PET Imaging of the Metabotropic Glutamate Receptor 5.
abstract: The metabotropic glutamate receptor 5 (mGluR5) is a high-interest target for PET imaging because it plays a role in several pathologies, including addiction, schizophrenia, and fragile X syndrome.
  
  
  METHODS
  We studied the pharmacokinetics of (18)F-FPEB (3-(18)F-fluoro-5-(2-pyridinylethynyl)benzonitrile), a selective PET radioligand for mGluR5, and used it to quantify mGluR5 in rat brain. Quantification was performed using both arterial sampling in combination with compartment models and simplified reference methods. The simplified reference tissue model (SRTM), Ichise's original multi-linear reference tissue model (MRTMO), and Logan noninvasive were tested as reference models with nondisplaceable binding (BPND) as outcome parameter. Additionally, test-retest scans were obtained in 6 animals.
  
  
  RESULTS
  (18)F-FPEB uptake in rat brain was consistent with its known distribution. No radiometabolites were present in the brain, and binding was specific as shown in blocking experiments, which also confirmed the cerebellum as a viable reference region. A 2-tissue-compartment model was used to determine BPND for the striatum (11.7 ± 1.5), nucleus accumbens (10.6 ± 2.0), hippocampus (9.0 ± 1.2), cortex (7.2 ± 1.0), and thalamus (4.0 ± 0.9). Reference methods were able to estimate these values with small bias (<2%). Test-retest analysis showed high repeatability between scans below 6%, also for shorter scan durations of 30 and 60 min.
  
  
  CONCLUSIONS
  Because of its favorable reversible kinetics, high specificity, and absence of brain radiometabolites (18)F-FPEB proves a highly useful tracer for in vivo visualization of the mGluR5 in rat brain. Moreover, reference tissue models allow noninvasive, rapid scanning with good test-retest.
authors.affiliation: KU Leuven-University of Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven, Belgium KU Leuven-University of Leuven/University Hospital Leuven, Division of Nuclear Medicine, Leuven, Belgium; and.
authors.forename: Bart
authors.initials: B
authors.lastname: de Laat
authors.affiliation: KU Leuven-University of Leuven/University Hospital Leuven, Division of Nuclear Medicine, Leuven, Belgium; and.
authors.forename: Gil
authors.initials: G
authors.lastname: Leurquin-Sterk
authors.affiliation: KU Leuven-University of Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven, Belgium KU Leuven-University of Leuven, Laboratory for Radiopharmacy, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
authors.affiliation: KU Leuven-University of Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven, Belgium KU Leuven-University of Leuven, Laboratory for Radiopharmacy, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.affiliation: KU Leuven-University of Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven, Belgium KU Leuven-University of Leuven/University Hospital Leuven, Division of Nuclear Medicine, Leuven, Belgium; and.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.affiliation: KU Leuven-University of Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven, Belgium KU Leuven-University of Leuven/University Hospital Leuven, Division of Nuclear Medicine, Leuven, Belgium; and.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: KU Leuven-University of Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven, Belgium KU Leuven-University of Leuven/University Hospital Leuven, Division of Nuclear Medicine, Leuven, Belgium; and cindy.casteels@med.kuleuven.be.
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging; D006624:Hippocampus / Q000000981:diagnostic imaging; D008297:Male; D009570:Nitriles / Q000493:pharmacokinetics; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: C527000:3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile; D009570:Nitriles; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5
keywords: 18F-FPEB; PET; kinetic modeling; metabotropic glutamate receptor 5; rat