title: Longitudinal Characterization of [18F]-FDG and [18F]-AV45 Uptake in the Double Transgenic TASTPM Mouse Model.
abstract: We aimed to monitor the timing of amyloid-β deposition in relation to changes in brain function using in vivo imaging with [18F]-AV45 and [18F]-FDG in a mouse model of Alzheimer's disease. TASTPM transgenic mice and wild-type controls were scanned longitudinally with [18F]-AV45 and [18F]-FDG before (3 months of age) and at multiple time points after the onset of amyloid deposition (6, 9, 12, and 15 months of age). As expected with increasing amyloidosis, TASTPM mice demonstrated progressive age-dependent increases in [18F]-AV45 uptake that were significantly higher than for WT from 9 months onwards and correlated to ex vivo measures of amyloid burden. The metabolism of [18F]-AV45 produces several brain penetrant radiometabolites and normalization to a reference region helps to negate this non-specific binding and improve the sensitivity of [18F]-AV45. The observed trajectory of [18F]-FDG alterations deviated from our proposed hypothesis of gradual decreases with worsening amyloidosis. While [18F]-FDG uptake in TASTPM mice was significantly lower than that of WT at 9 months, reduced [18F]-FDG was not associated with aging in TASTPM mice. Moreover, [18F]-FDG uptake did not correlate to measures of ex vivo amyloid burden. Our findings suggest that while amyloid-β is sufficient to induce hypometabolism, these pathologies are not linked in a dose-dependent manner in TASTPM mice.
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Waldron
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Department of Nuclear Medicine, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Verhaeghe
authors.affiliation: R&D China U.K. Group, GlaxoSmithKline, Stevenage, UK.
authors.forename: Jill C
authors.initials: JC
authors.lastname: Richardson
authors.affiliation: Department of Neuroscience, Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Department of Nuclear Medicine, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.affiliation: Department of Neuroscience, Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Langlois
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D005026:Ethylene Glycols / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics; D013997:Time Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D005026:Ethylene Glycols; C508853:PSEN1 protein, human; D053764:Presenilin-1; D019788:Fluorodeoxyglucose F18; C545186:florbetapir
keywords: Alzheimer’s disease; [18F]-AV45; [18F]-FDG; longitudinal; small animal imaging; transgenic mice