title: Kinetic modeling and long-term test-retest reproducibility of the mGluR5 PET tracer 18F-FPEB in human brain.
abstract: (18)F-FPEB is a promising PET tracer for studying the metabotropic glutamate subtype 5 receptor (mGluR5) expression in neuropsychiatric disorders. To assess the potential of (18)F-FPEB for longitudinal mGluR5 evaluation in patient studies, we evaluated the long-term test-retest reproducibility using various kinetic models in the human brain. Nine healthy volunteers underwent consecutive scans separated by a 6-month period. Dynamic PET was combined with arterial sampling and radiometabolite analysis. Total distribution volume (V(T)) and nondisplaceable binding potential (BP(ND)) were derived from a two-tissue compartment model without constraints (2TCM) and with constraining the K(1)/k(2) ratio to the value of either cerebellum (2TCM-CBL) or pons (2TCM-PONS). The effect of fitting different functions to the tracer parent fractions and reducing scan duration were assessed. Regional absolute test-retest variability (aTRV), coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were computed. The 2TCM-CBL showed best fits. The mean 6-month aTRV of V(T) ranged from 8 to 13% (CR < 25%) with ICC > 0.6 for all kinetic models. BPND from 2TCM-CBL with a sigmoid fit for the parent fractions showed the best reproducibility, with aTRV ≤ 7% (CR < 16%) and ICC > 0.9 in most regions. Reducing the scan duration from 90 to 60 min did not affect reproducibility. These results demonstrate for the first time that (18)F-FPEB brain PET has good long-term reproducibility, therefore validating its use to monitor mGluR5 expression in longitudinal clinical studies. We suggest a 2TCM-CBL with fitting a sigmoid function to the parent fractions to be optimal for this tracer.
authors.affiliation: Division of Nuclear Medicine, KU Leuven - University of Leuven and University Hospital Leuven, Herestraat 49, Leuven, 3000, Belgium.
authors.forename: Gil
authors.initials: G
authors.lastname: Leurquin-Sterk
authors.affiliation: Division of Nuclear Medicine, KU Leuven - University of Leuven and University Hospital Leuven, Herestraat 49, Leuven, 3000, Belgium.
authors.forename: Andrey
authors.initials: A
authors.lastname: Postnov
authors.affiliation: Division of Nuclear Medicine, KU Leuven - University of Leuven and University Hospital Leuven, Herestraat 49, Leuven, 3000, Belgium.|MoSAIC, Molecular Small Animal Imaging Center, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: de Laat
authors.affiliation: Division of Nuclear Medicine, KU Leuven - University of Leuven and University Hospital Leuven, Herestraat 49, Leuven, 3000, Belgium.|MoSAIC, Molecular Small Animal Imaging Center, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.affiliation: Laboratory for Radiopharmacy, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
authors.affiliation: Toxicological Center, University of Antwerp, Antwerp, Belgium.
authors.forename: Cleo L
authors.initials: CL
authors.lastname: Crunelle
authors.affiliation: Laboratory for Radiopharmacy, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.affiliation: Division of Nuclear Medicine, KU Leuven - University of Leuven and University Hospital Leuven, Herestraat 49, Leuven, 3000, Belgium.|MoSAIC, Molecular Small Animal Imaging Center, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.affiliation: Division of Nuclear Medicine, KU Leuven - University of Leuven and University Hospital Leuven, Herestraat 49, Leuven, 3000, Belgium.|MoSAIC, Molecular Small Animal Imaging Center, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000592:standards; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D018691:Excitatory Amino Acid Antagonists; C578935:GRM5 protein, human; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5
keywords: 18F-FPEB; kinetic modelling; mGluR5; positron emission tomography; test-retest reproducibility