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Imaging beta-amyloid deposition in transgenic mouse models of Alzheimer's diseae with 18F flutemetamol PET

Haaparanta-Solin, Merja and Snellman, Annijna and Rokka, Johanna and Lopez-Picon, Francisco and Eskola, Olli and Salmona, Mario and Forloni, GianLiigi and Schienin, Mika and Rinne, Juha (2014) Imaging beta-amyloid deposition in transgenic mouse models of Alzheimer's diseae with 18F flutemetamol PET. EJNMMI Res..

Abstract

Purpose We evaluated the potential of the high specific radioactivity [18F]flutemetamol, for detecting changes in beta amyloid (Abeta) deposition in vivo with transgenic APP23, Tg2576, and APPswe-PS1dE9 mouse models of Alzheimer’s disease (AD).
Methods [18F]flutemetamol uptake in mouse brain was evaluated in vivo at ages 9-22 months with Inveon Multimodality PET/CT. [18F]Flutemetamol retention in the frontal cortex (FC) was evaluated by Logan distribution volume ratios (DVR) and ratios to cerebellum (FC/CB) during a late washout phase (50-60 min). In addition, specific [18F]flutemetamol binding to Abeta was evaluated in brain slices in vitro and by ex vivo autoradiography. The amounts of Abeta were estimated with histological and immunohistochemical staining.
Results In APP23 mice, [18F]flutemetamol retention increased with age in the FC. The FC/CB50-60 increased from 0.81 and 0.89 at 9 months (N = 2), to 1.16 and 1.35 at 18 months (N = 2), and 1.31 at 21 months (N = 1). [18F]flutemetamol binding co-localized with Abeta in brain slices examined in vitro and ex vivo. For Tg2576 mice, the FC/CB50-60 and DVRs also showed an increasing trend. Plaque loads were modest, but [18F]flutemetamol specifically bound to Abeta in brain slices studied in vitro and ex vivo. In APPswe-PS1dE9 mice, DVRs and FC/CB50-60 did not increase with age. Abeta deposits were visible also in the CB at 19 months.
Conclusion Increased [18F]flutemetamol retention in the brain in vivo was detected in APP23 mice. The high specific radioactivity of [18F]flutemetamol did not provide a notable advantage in detecting Abeta compared to [11C]PIB.

Item Type: Article
Keywords: Alzheimer’s disease, [18F]flutemetamol, Preclinical evaluation, β-amyloid, transgenic mouse model, small animal PET
Date Deposited: 04 May 2016 23:45
Last Modified: 04 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/21340

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