Radioiodinated aza-diphenylacetylenes as potential SPECT imaging agents for β-amyloid plaque detection

Wenchao Qu, Mei Ping Kung, Catherine Hou, Lee-Way Jin, Hank F. Kung

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Two new iodinated fluoro- and hydroxy-pegylated aza-diphenylacetylene derivatives, 1 and 2, targeting β-amyloid (Aβ) plaques have been successfully prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [125I]IMPY (6-iodo-2-(4′-dimethylamino)phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good binding affinities (Ki = 9.2 and 16.8 nM for 1 and 2, respectively). Brain penetrations of the corresponding radioiodinated ligands, evaluated in the normal mice, showed good initial brain penetrations (3.55% and 5.67% ID/g for [125I]1 and [125I]2 at 2 min post-injection). The washout from normal mice brain was relatively fast (0.33% and 0.91% ID/g at 2 h post-injection). The specific binding of these radioiodinated ligands to β-amyloid plaques was clearly demonstrated using film autoradiography of AD brain sections. Taken together, these preliminary results strongly suggest that these novel iodinated aza-diphenylacetylenes may be potentially useful for imaging Aβ plaques in the living human brain.

Original languageEnglish (US)
Pages (from-to)3581-3584
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number13
DOIs
StatePublished - Jul 1 2007

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Keywords

  • Alzheimer's disease
  • Autoradiography and Sonogashira coupling reaction
  • Biodistribution
  • Radioiodination

ASJC Scopus subject areas

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

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