A Metal-Free Method for Producing MRI Contrast at Amyloid-β

Silvia Hilt, Tang Tang, Jeffrey H. Walton, Madhu Budamagunta, Izumi Maezawa, T. Kalai, Kálmán Hideg, Vikrant Singh, Heike Wulff, Qizhi Gong, Lee Way Jin, Angelique Louie, John C. Voss

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by depositions of the amyloid-β (Aβ) peptide in the brain. The disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. It is therefore imperative to develop methods that permit early detection and monitoring of disease progression. In addition, the multifactorial pathogenesis of AD has identified several potential avenues for AD intervention. Thus, evaluation of therapeutic candidates over lengthy trial periods also demands a practical, noninvasive method for measuring Aβ in the brain. Magnetic resonance imaging (MRI) is the obvious choice for such measurements, but contrast enhancement for Aβ has only been achieved using Gd(III)-based agents. There is great interest in gadolinium-free methods to image the brain. In this study, we provide the first demonstration that a nitroxide-based small-molecule produces MRI contrast in brain specimens with elevated levels of Aβ. The molecule is comprised of a fluorene (a molecule with high affinity for Aβ) and a nitroxide spin label (a paramagnetic MRI contrast species). Labeling of brain specimens with the spin-labeled fluorene produces negative contrast in samples from AD model mice whereas no negative contrast is seen in specimens harvested from wild-type mice. Injection of spin-labeled fluorene into live mice resulted in good brain penetration, with the compound able to generate contrast 24-h post injection. These results provide a proof of concept method that can be used for early, noninvasive, gadolinium-free detection of amyloid plaques by MRI.

Original languageEnglish
Pages (from-to)1667-1681
Number of pages15
JournalJournal of Alzheimer's Disease
Volume55
Issue number4
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Alzheimer's disease
  • amyloid MRI contrast
  • amyloid-β
  • magnetic resonance imaging
  • nitroxide spin label
  • spin-labeled fluorene

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Hilt, S., Tang, T., Walton, J. H., Budamagunta, M., Maezawa, I., Kalai, T., Hideg, K., Singh, V., Wulff, H., Gong, Q., Jin, L. W., Louie, A., & Voss, J. C. (2017). A Metal-Free Method for Producing MRI Contrast at Amyloid-β. Journal of Alzheimer's Disease, 55(4), 1667-1681. https://doi.org/10.3233/JAD-160279