Cross-sectional comparison of small animal [18F]-florbetaben amyloid-PET between transgenic AD mouse models

PLoS One. 2015 Feb 23;10(2):e0116678. doi: 10.1371/journal.pone.0116678. eCollection 2015.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds*
  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Cross-Sectional Studies
  • Disease Models, Animal
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid / diagnostic imaging*
  • Plaque, Amyloid / metabolism
  • Positron-Emission Tomography
  • Stilbenes*

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Stilbenes
  • 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Grants and funding

The study was financially supported by the SyNergy Cluster, Core 2 Project. During this study, K. B. received funding in the form of salary from F. Hoffmann-La Roche. P. B. received consultant fees from GE and Piramal Imaging, as well as honoraria from Siemens. A. R. received consultant fees from Piramal Imaging and GE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.