Styrylbenzoxazole Derivatives for In Vivo Imaging Amyloid Plaques in the Brain

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

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)2535-2541
Number of pages7
JournalJournal of Neuroscience
Volume24
Issue number10
DOIs
Publication statusPublished - 2004 Mar 10

Keywords

  • Alzheimer's disease
  • Amyloid-β protein
  • Imaging
  • Neurofibrillary tangles
  • Positron emission tomography
  • Senile plaques

ASJC Scopus subject areas

  • Neuroscience(all)

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