Novel 18F-labeled benzoxazole derivatives as potential positron emission tomography probes for imaging of cerebral β-amyloid plaques in alzheimers disease

Mengchao Cui, Masahiro Ono, Hiroyuki Kimura, Masashi Ueda, Yuji Nakamoto, Kaori Togashi, Yoko Okamoto, Masafumi Ihara, Ryosuke Takahashi, Boli Liu, Hideo Saji

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34 Citations (Scopus)


Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[ 18F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N- methylaniline ([ 18F]24) and 4-(5-(2-(2-(2-[ 18F] fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([ 18F]32), were synthesized and evaluated as probes for imaging cerebral β-amyloid (Aβ) plaques in living brain tissue by PET. [ 18F]24 and [ 18F]32 displayed high affinity for Aβ 1-42 aggregates (K i = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [ 18F]24 also displayed excellent binding to Aβ plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [ 18F]24 between Tg2576 and wild-type mice. The results suggest [ 18F]24 to be a useful PET agent for detecting Aβ plaques in the living human brain.

Original languageEnglish
Pages (from-to)9136-9145
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number21
Publication statusPublished - Nov 8 2012
Externally publishedYes


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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