Synthesis and biological evaluation of novel technetium-99m labeled phenylbenzoxazole derivatives as potential imaging probes for β-amyloid plaques in brain

Xuedan Wang, Mengchao Cui, Pingrong Yu, Zijing Li, Yanping Yang, Hongmei Jia, Boli Liu

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26 Scopus citations

Abstract

Two uncharged 99mTc-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for β-amyloid plaques. The 99mTc and corresponding rhenium complexes were synthesized by coupling monoamine-monoamide dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9 selectively stainined the β-amyloid plaques on the sections of transgenic mouse, and showed high affinity for Aβ (1-42) aggregates (K i = 11.1 nM and 14.3 nM, respectively). Autoradiography in vitro indicated that [ 99mTc]6 clearly labeled β-amyloid plaques on the sections of transgenic mouse. Biodistribution experiments in normal mice revealed that [ 99mTc]6 displayed moderate initial brain uptake (0.81% ID/g at 2 min), and quickly washed out from the brain (0.25% ID/g at 60 min). The preliminary results indicate that the properties of [ 99mTc]6 are promising, although additional refinements are needed to improve the ability to cross the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)4327-4331
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number13
DOIs
StatePublished - Jul 1 2012

Keywords

  • β-Amyloid plaque
  • Alzheimer's disease
  • Imaging probe
  • Phenylbenzoxazole
  • Technetium-99m

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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