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

TitleA Metal-Free Method for Producing MRI Contrast at Amyloid-β.
Publication TypeJournal Article
Year of Publication2017
AuthorsHilt, S, Tang, T, Walton, JH, Budamagunta, M, Maezawa, I, Kálai, T, Hideg, K, Singh, V, Wulff, H, Gong, Q, Jin, L-W, Louie, A, Voss, JC
JournalJ Alzheimers Dis
Volume55
Issue4
Pagination1667-1681
Date Published2017
ISSN1875-8908
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.

DOI10.3233/JAD-160279
Alternate JournalJ. Alzheimers Dis.
PubMed ID27911291
PubMed Central IDPMC5718836
Grant ListP30 AG010129 / AG / NIA NIH HHS / United States
R01 EB000993 / EB / NIBIB NIH HHS / United States
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Source URL: https://www.j-alz.com/content/metal-free-method-producing-mri-contrast-amyloid-%CE%B2