In vivo detection of amyloid β deposition using 19F magnetic resonance imaging with a 19F-containing curcumin derivative in a mouse model of Alzheimer's disease

Yanagisawa, Daijiro; Amatsubo, Tomone; Morikawa, Shigehiro; Taguchi, Hiroyasu; Urushitani, Makoto; Shirai, Nobuyuki; Hirao, Koichi; Shiino, Akihiko; Inubushi, Toshiro; Tooyama, Ikuo

doi:10.1016/j.neuroscience.2011.03.071

Cited by 83 publications

(78 citation statements)

References 27 publications

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“…Apart from contrast enhancement, an analogous approach has been developed for 19 F-labeled agents using chemical shift imaging (CSI). In this work, a 19 F-labeled curcumin derivative was found to accumulate in the brains of AD model mice sufficient for CSI mapping [41]. As our knowledge on the distribution, specificity and tolerance of small-molecule Aβ targeting agents becomes more complete, one can envision a multimodal MR-based approach for measuring amyloid in the brain.…”

Section: Discussionmentioning

confidence: 99%

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

Hilt

Tang

Walton

et al. 2016

JAD

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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 SLF into live mice resulted in good brain penetration, with the compound able to generate contrast 24-hr post injection. These results provide a proof of concept method that can be used for early, noninvasive, gadolinium-free detection of amyloid plaques by magnetic resonance imaging (MRI).

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Section: Discussionmentioning

confidence: 99%

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

Hilt

Tang

Walton

et al. 2016

JAD

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“…With a log p value of 2.9, curcumin is insoluble in any physiological aqueous condition suitable for in vivo application [33]. Therefore, it must be dissolved in saline with a high proportion of methanol [33] or Tween [16]. In congruence with significant mortality associated with iv injection of curcumin noted our study, bolus administration of a viscous solution like that used to administer curcumin can be fatal.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, we recently developed a perfluoro curcumin analog (FMeC1) for 19 F NMR imaging (Fig. 1) to facilitate in vivo visualization of the mechanism that enables curcumin to bind to Aβ [16]. As with many Aβ aggregation inhibitors, however, the clinical utility of curcumin therapy has been severely limited due to its poor aqueous solubility and relatively low penetration across the BBB [11, 17, 18].…”

Section: Introductionmentioning

confidence: 99%

Inhalable Curcumin: Offering the Potential for Translation to Imaging and Treatment of Alzheimer's Disease

McClure

Yanagisawa

Stec

et al. 2015

JAD

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Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer’s disease. Beyond its ability to bind to amyloidal plaques, the compound can also cross the blood brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use. Here, we describe a novel technique to aerosolize a curcumin derivative, FMeC1 and facilitate its safe delivery to the brain. Aside from the translational applicability of this approach, a study in the 5XFAD mouse model suggested that inhalation exposure to an aerosolized FMeC1 modestly improved the distribution of the compound in the brain. Additionally, immunohistochemistry data confirms that following aerosol delivery, FMeC1 binds amyloidal plaques expressed in the hippocampal areas and cortex.

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“…MR amyloid imaging can be expected to further advance, with ongoing developments in amyloid specific MR contrast agents. For example, a novel recent approach taken by Higuchi et al (2005) and further developed by Yanagisawa et al (2011) involved labeling amyloid with 19 F-containing compounds. As biological tissues contain no 19 F, detection of plaques can be improved by reduction in the background non-specific signal (Higuchi et al, 2005; Yanagisawa et al, 2011).…”

Section: Translating Neuroimaging: Understanding and Integrating Pathmentioning

confidence: 99%

A review of Î²-amyloid neuroimaging in Alzheimer's disease

et al. 2014

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Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments. Neuroimaging has enabled in vivo visualization of pathological changes in the brain associated with the disease, providing a greater understanding of its pathophysiological development and progression. However, neuroimaging biomarkers do not yet offer clear advantages over current clinical diagnostic criteria for them to be accepted into routine clinical use. Nonetheless, current insights from neuroimaging combined with the elucidation of biochemical and molecular processes in AD are informing the ongoing development of new imaging techniques and their application. Much of this research has been greatly assisted by the availability of transgenic mouse models of AD. In this review we summarize the main efforts of neuroimaging in AD in humans and in mouse models, with a specific focus on β-amyloid, and discuss the potential of new applications and novel approaches.

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In vivo detection of amyloid β deposition using 19F magnetic resonance imaging with a 19F-containing curcumin derivative in a mouse model of Alzheimer's disease

Cited by 83 publications

References 27 publications

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

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

Inhalable Curcumin: Offering the Potential for Translation to Imaging and Treatment of Alzheimer's Disease

A review of Î²-amyloid neuroimaging in Alzheimer's disease

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