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

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

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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