Technetium-99m labeled pyridyl benzofuran derivatives as single photon emission computed tomography imaging probes for β-amyloid plaques in Alzheimer's brains

Yan Cheng, Masahiro Ono, Hiroyuki Kimura, Masashi Ueda, Hideo Saji

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52 Citations (Scopus)

Abstract

Three novel 99mTc-labeled pyridyl benzofuran derivatives were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography (SPECT). The 99mTc and corresponding rhenium complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. All Re complexes showed affinity for Aβ(1-42) aggregates (K i = 13.6-149.6 nM). Biodistribution experiments in normal mice revealed that the 99mTc-labeled derivatives displayed sufficient uptake in the brain (1.41-1.80% ID/g at 2 min postinjection). Notably, [ 99mTc]BAT-Bp-2 showed a good initial uptake (1.80% ID/g at 2 min) and a reasonable washout from the brain (0.79% ID/g at 60 min). Ex vivo autoradiography with [ 99mTc]BAT-Bp-2 revealed substantial labeling of β-amyloid plaques in sections of brain tissue from Tg2576 transgenic mice but not in the age-matched controls. [ 99mTc]BAT-Bp-2 may be a potential SPECT probe for imaging β-amyloid plaques in Alzheimer's brains.

Original languageEnglish
Pages (from-to)2279-2286
Number of pages8
JournalJournal of medicinal chemistry
Volume55
Issue number5
DOIs
Publication statusPublished - Mar 8 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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