In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimer's disease with a high specific activity PET imaging agent [18F]flutemetamol

Anniina Snellman, Johanna Rokka, Francisco R. López-Picón, Olli Eskola, Mario Salmona, Gianluigi Forloni, Mika Scheinin, Olof Solin, Juha O. Rinne, Merja Haaparanta-Solin

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The purpose of the study was to evaluate the applicability of 18F-labelled amyloid imaging positron emission tomography (PET) agent [18F]flutemetamol to detect changes in brain beta-amyloid (Aβ) deposition in vivo in APP23, Tg2576 and APPswe-PS1dE9 mouse models of Alzheimer's disease. We expected that the high specific activity of [18F]flutemetamol would make it an attractive small animal Aβ imaging agent. Methods: [18F]flutemetamol uptake in the mouse brain was evaluated in vivo at 9 to 22 months of age with an Inveon Multimodality PET/CT camera (Siemens Medical Solutions USA, Knoxville, TN, USA). Retention in the frontal cortex (FC) was evaluated by Logan distribution volume ratios (DVR) and FC/cerebellum (CB) ratios during the late washout phase (50 to 60 min). [18F]flutemetamol binding to Aβ was also evaluated in brain slices by in vitro and ex vivo autoradiography. The amount of Aβ in the brain slices was determined with Thioflavin S and anti-Aβ1−40 immunohistochemistry. Results: In APP23 mice, [18F]flutemetamol retention in the FC increased from 9 to 18 months. In younger mice, DVR and FC/CB50-60 were 0.88 (0.81) and 0.88 (0.89) at 9 months (N = 2), and 0.98 (0.93) at 12 months (N = 1), respectively. In older mice, DVR and FC/CB50-60 were 1.16 (1.15) at 15 months (N = 1), 1.13 (1.16) and 1.35 (1.35) at 18 months (N = 2), and 1.05 (1.31) at 21 months (N = 1). In Tg2576 mice, DVR and FC/CB50-60 showed modest increasing trends but also high variability. In APPswe-PS1dE9 mice, DVR and FC/CB50-60 did not increase with age. Thioflavin S and anti-Aβ1−40 positive Aβ deposits were present in all transgenic mice at 19 to 22 months, and they co-localized with [18F]flutemetamol binding in the brain slices examined with in vitro and ex vivo autoradiography. Conclusions: Increased [18F]flutemetamol retention in the brain was detected in old APP23 mice in vivo. However, the high specific activity of [18F]flutemetamol did not provide a notable advantage in Tg2576 and APPswe-PS1dE9 mice compared to the previously evaluated structural analogue [11C]PIB. For its practical benefits, [18F]flutemetamol imaging with a suitable mouse model like APP23 is an attractive alternative.

Original languageEnglish
Article number37
Pages (from-to)1-11
Number of pages11
JournalEJNMMI Research
Volume4
Issue number1
DOIs
Publication statusPublished - Aug 1 2014

Keywords

  • Alzheimer's disease
  • Amyloid imaging
  • APP23
  • APPswe-PS1dE9
  • Beta-amyloid
  • High specific activity
  • Preclinical evaluation
  • Tg2576
  • Transgenic mouse model
  • [F]flutemetamol

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimer's disease with a high specific activity PET imaging agent [<sup>18</sup>F]flutemetamol'. Together they form a unique fingerprint.

Cite this