TY - JOUR
T1 - Styrylbenzoxazole Derivatives for In Vivo Imaging Amyloid Plaques in the Brain
AU - Okamura, Nobuyuki
AU - Suemoto, Takahiro
AU - Shimadzu, Hiroshi
AU - Suzuki, Masako
AU - Shiomitsu, Tsuyoshi
AU - Akatsu, Hiroyasu
AU - Yamamoto, Takayuki
AU - Staufenbiel, Matthias
AU - Yanai, Kazuhiko
AU - Arai, Hiroyuki
AU - Sasaki, Hidetada
AU - Kudo, Yukitsuka
AU - Sawada, Tohru
PY - 2004/3/10
Y1 - 2004/3/10
N2 - 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-β (Aβ) 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 Aβ1-42-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, 18F-radiolabeled BF-168 demonstrated abundant initial brain uptake (3.9% injected dose/gm at 2 min after injection) and fast clearance (t1/2 = 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 [18F]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.
AB - 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-β (Aβ) 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 Aβ1-42-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, 18F-radiolabeled BF-168 demonstrated abundant initial brain uptake (3.9% injected dose/gm at 2 min after injection) and fast clearance (t1/2 = 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 [18F]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.
KW - Alzheimer's disease
KW - Amyloid-β protein
KW - Imaging
KW - Neurofibrillary tangles
KW - Positron emission tomography
KW - Senile plaques
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UR - http://www.scopus.com/inward/citedby.url?scp=12144289490&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4456-03.2004
DO - 10.1523/JNEUROSCI.4456-03.2004
M3 - Article
C2 - 15014129
AN - SCOPUS:12144289490
VL - 24
SP - 2535
EP - 2541
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 10
ER -