title: Cross-sectional comparison of small animal [18F]-florbetaben amyloid-PET between transgenic AD mouse models.
abstract: We aimed to compare [18F]-florbetaben PET imaging in four transgenic mouse strains modelling Alzheimer's disease (AD), with the main focus on APPswe/PS2 mice and C57Bl/6 mice serving as controls (WT). A consistent PET protocol (N = 82 PET scans) was used, with cortical standardized uptake value ratio (SUVR) relative to cerebellum as the endpoint. We correlated methoxy-X04 staining of β-amyloid with PET results, and undertook ex vivo autoradiography for further validation of a partial volume effect correction (PVEC) of PET data. The SUVR in APPswe/PS2 increased from 0.95±0.04 at five months (N = 5) and 1.04±0.03 (p<0.05) at eight months (N = 7) to 1.07±0.04 (p<0.005) at ten months (N = 6), 1.28±0.06 (p<0.001) at 16 months (N = 6) and 1.39±0.09 (p<0.001) at 19 months (N = 6). SUVR was 0.95±0.03 in WT mice of all ages (N = 22). In APPswe/PS1G384A mice, the SUVR was 0.93/0.98 at five months (N = 2) and 1.11 at 16 months (N = 1). In APPswe/PS1dE9 mice, the SUVR declined from 0.96/0.96 at 12 months (N = 2) to 0.91/0.92 at 24 months (N = 2), due to β-amyloid plaques in cerebellum. PVEC reduced the discrepancy between SUVR-PET and autoradiography from -22% to +2% and increased the differences between young and aged transgenic animals. SUVR and plaque load correlated highly between strains for uncorrected (R = 0.94, p<0.001) and PVE-corrected (R = 0.95, p<0.001) data. We find that APPswe/PS2 mice may be optimal for longitudinal amyloid-PET monitoring in planned interventions studies.
authors.affiliation: Dept. of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brendel
authors.affiliation: Dept. of Translational Research I, German Center for Neurodegenerative Diseases (DZNE)-site Munich, University of Munich, Munich, Germany; Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaworska
authors.affiliation: Dept. of Translational Research I, German Center for Neurodegenerative Diseases (DZNE)-site Munich, University of Munich, Munich, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Grießinger
authors.affiliation: Dept. of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rötzer
authors.affiliation: Dept. of Translational Research I, German Center for Neurodegenerative Diseases (DZNE)-site Munich, University of Munich, Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Burgold
authors.affiliation: Dept. of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Gildehaus
authors.affiliation: Dept. of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Janette
authors.initials: J
authors.lastname: Carlsen
authors.affiliation: Department of Nuclear Medicine, University of Erlangen, Erlangen, Germany; Department of Neuroscience and Pharmacology, Copenhagen University, Copenhagen, Denmark.
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Baumann
authors.affiliation: Adolf-Butenandt-Institute, Biochemistry, University of Munich, Munich, Germany; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.affiliation: Adolf-Butenandt-Institute, Biochemistry, University of Munich, Munich, Germany; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Steiner
authors.affiliation: Dept. of Nuclear Medicine, University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Dept. of Translational Research I, German Center for Neurodegenerative Diseases (DZNE)-site Munich, University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.affiliation: Dept. of Nuclear Medicine, University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Rominger
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D013267:Stilbenes
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013267:Stilbenes; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene