In-vitro and in-vivo characterization of CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of amyloid-beta deposits in Alzheimer mice

  • Photoacoustics. 2021 Jul 15:23:100285. doi: 10.1016/j.pacs.2021.100285.
Ruiqing Ni  1  2  3 ,  Alessia Villois  4 ,  Xose Luis Dean-Ben  1  5 ,  Zhenyue Chen  1  5 ,  Markus Vaas  1 ,  Stavros Stavrakis  4 ,  Gloria Shi  1 ,  Andrew deMello  4 ,  Chongzhao Ran  6 ,  Daniel Razansky  1  3  5 ,  Paolo Arosio  4 ,  Jan Klohs  1  3
Affiliations
  • 1. Institute for Biomedical Engineering, ETH & University of Zurich, Zurich, Switzerland.
  • 2. Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
  • 3. Zurich Neuroscience Center (ZNZ), Zurich, Switzerland.
  • 4. Institute for Chemical and Bioengineering, Department of Chemistry, ETH Zurich, Zurich, Switzerland.
  • 5. Institute of Pharmacology and Toxicology, University of Zurich, Switzerland.
  • 6. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
PMID: 34354924 DOI: 10.1016/j.pacs.2021.100285
Abstract

The abnormal deposition of fibrillar beta-amyloid (Aβ) deposits in the brain is one of the major histopathological hallmarks of Alzheimer's disease (AD). Here, we characterized curcumin-derivative CRANAD-2 for multi-spectral optoacoustic tomography and fluorescence imaging of brain Aβ deposits in the arcAβ mouse model of AD cerebral amyloidosis. CRANAD-2 showed a specific and quantitative detection of Aβ fibrils in vitro, even in complex mixtures, and it is capable of distinguishing between monomeric and fibrillar forms of Aβ. In vivo epi-fluorescence microscopy and optoacoustic tomography after intravenous CRANAD-2 administration demonstrated higher cortical retention in arcAβ compared to non-transgenic littermate mice. Immunohistochemistry showed co-localization of CRANAD-2 and Aβ deposits in arcAβ mouse brain sections, thus verifying the specificity of the probe. In conclusion, we demonstrate suitability of CRANAD-2 for optical detection of Aβ deposits in animal models of AD pathology, which facilitates mechanistic studies and the monitoring of putative treatments targeting Aβ deposits.

Keywords
Alzheimer’s disease; Amyloid-beta; Animal model; Fluorescence imaging; Multi-spectral optoacoustic tomography.
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