Abstract |
Progressive deposition of senile plaques (SPs) is one of the major neuropathological features of Alzheimer's disease (AD) that precedes cognitive decline. Noninvasive detection of SPs could, therefore, be a potential diagnostic test for early detection of AD patients. For imaging SPs in the living brain, we have developed a series of styrylbenzoxazole derivatives that achieve high binding affinity for amyloid-beta (Abeta) fibrils. One of these compounds, 6-(2-Fluoroethoxy)-2-[2-(4-methylaminophenil) ethenyl] benzoxazole (BF-168), selectively binds SPs in AD brain sections and recognizes Abeta1-42-positive diffuse plaques as well as neuritic plaques in AD brain sections. Intravenous injection of BF-168 in PS1/APP and APP23 transgenic mice resulted in specific in vivo labeling to both compact and diffuse amyloid deposits in the brain. In addition, (18)F-radiolabeled BF-168 demonstrated abundant initial brain uptake (3.9% injected dose/gm at 2 min after injection) and fast clearance (t(1/2) = 24.7 min) after intravenous administration in normal mice. Furthermore, autoradiograms of brain sections from APP23 transgenic mice at 180 min after intravenous injection of [(18)F] BF-168 showed selective labeling of brain amyloid deposits with little nonspecific binding. These findings strongly suggest that styrylbenzoxazole derivatives are promising candidate probes for positron emission tomography and single-photon emission computed tomography imaging for early detection of amyloid plaque formation.
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Authors | Nobuyuki Okamura, Takahiro Suemoto, Hiroshi Shimadzu, Masako Suzuki, Tsuyoshi Shiomitsu, Hiroyasu Akatsu, Takayuki Yamamoto, Matthias Staufenbiel, Kazuhiko Yanai, Hiroyuki Arai, Hidetada Sasaki, Yukitsuka Kudo, Tohru Sawada |
Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience
(J Neurosci)
Vol. 24
Issue 10
Pg. 2535-41
(Mar 10 2004)
ISSN: 1529-2401 [Electronic] United States |
PMID | 15014129
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 6-(2-fluoroethoxy)-2-(2-(4-methylaminophenil)ethenyl)benzoxazole
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Aniline Compounds
- Benzoxazoles
- Fluorine Radioisotopes
- Macromolecular Substances
- Peptide Fragments
- amyloid beta-protein (1-40)
- amyloid beta-protein (1-42)
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Topics |
- Alzheimer Disease
(diagnostic imaging, metabolism)
- Amyloid beta-Peptides
(chemistry, metabolism)
- Amyloid beta-Protein Precursor
(genetics)
- Aniline Compounds
(metabolism, pharmacokinetics)
- Animals
- Autoradiography
- Benzoxazoles
(metabolism, pharmacokinetics)
- Binding, Competitive
(drug effects)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Fluorine Radioisotopes
- Humans
- Injections, Intravenous
- Macromolecular Substances
- Mice
- Mice, Transgenic
- Peptide Fragments
(chemistry, metabolism)
- Plaque, Amyloid
(diagnostic imaging, metabolism)
- Sensitivity and Specificity
- Tomography, Emission-Computed
(methods)
- Tomography, Emission-Computed, Single-Photon
(methods)
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