title: Longitudinal assessment of cerebral β-amyloid deposition in mice overexpressing Swedish mutant β-amyloid precursor protein using 18F-florbetaben PET.
abstract: The progression of β-amyloid deposition in the brains of mice overexpressing Swedish mutant β-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel β-amyloid tracer (18)F-florbetaben.
  
  
  METHODS
  Groups of APP-Swe and age-matched wild-type (WT) mice (age range, 10-20 mo) were investigated. Dynamic emission recordings were acquired with a small-animal PET scanner during 90 min after the administration of (18)F-florbetaben (9 MBq, intravenously). After spatial normalization of individual PET recordings to common coordinates for mouse brain, binding potentials (BPND) and standardized uptake value ratios (SUVRs) were calculated relative to the cerebellum. Voxelwise analyses were performed using statistical parametric mapping (SPM). Histochemical analyses and ex vivo autoradiography were ultimately performed in a subset of animals as a gold standard assessment of β-amyloid plaque load.
  
  
  RESULTS
  SUVRs calculated from static recordings during the interval of 30-60 min after tracer injection correlated highly with estimates of BPND based on the entire dynamic emission recordings. (18)F-florbetaben binding did not significantly differ in APP-Swe mice and WT animals at 10 and 13 mo of age. At 16 mo of age, the APP-Swe mice had a significant 7.9% increase (P < 0.01) in cortical (18)F-florbetaben uptake above baseline and at 20 mo there was a 16.6% increase (P < 0.001), whereas WT mice did not show any temporal changes in tracer uptake during the interval of follow-up. Voxelwise SPM analyses revealed the first signs of increased cortical binding at 13 mo and confirmed progressive binding increases in both the frontal and the temporal cortices (P < 0.001 uncorrected) to 20 mo. The SUVR strongly correlated with percentage plaque load (R = 0.95, P < 0.001).
  
  
  CONCLUSIONS
  In the first longitudinal PET study in an AD mouse model using the novel β-amyloid tracer (18)F-florbetaben, the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice were sensitively monitored. This method should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany. axel.rominger@med.uni-muenchen.de
authors.forename: Axel
authors.initials: A
authors.lastname: Rominger
authors.forename: Matthias
authors.initials: M
authors.lastname: Brendel
authors.forename: Steffen
authors.initials: S
authors.lastname: Burgold
authors.forename: Kevin
authors.initials: K
authors.lastname: Keppler
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Baumann
authors.forename: Guoming
authors.initials: G
authors.lastname: Xiong
authors.forename: Erik
authors.initials: E
authors.lastname: Mille
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Gildehaus
authors.forename: Janette
authors.initials: J
authors.lastname: Carlsen
authors.forename: Juli
authors.initials: J
authors.lastname: Schlichtiger
authors.forename: Sabrina
authors.initials: S
authors.lastname: Niedermoser
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Harald
authors.initials: H
authors.lastname: Steiner
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D008137:Longitudinal Studies; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013267:Stilbenes / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013267:Stilbenes; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
keywords: 18F-florbetaben; Alzheimer disease; small-animal PET; transgenic mouse model; β-amyloid plaque load