New diphenylacetylenes as probes for positron emission tomographic imaging of amyloid plaques

Rajesh Chandra, Shunichi Oya, Mei Ping Kung, Catherine Hou, Lee-Way Jin, Hank F. Kung

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

A series of 18F fluoropegylated diphenylacetylenes as probes for binding to Aβ plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b, 14a, and 14b, displayed high binding affinities in postmortem AD brain homogenates (Ki ranging from 1.2 to 2.9 nM). In vivo biodistribution in normal mice exhibited excellent initial brain penetrations (4.42, 4.55, 5.41, and 6.78% dose/g at 2 min for [ 18F]12a, 12b, 14a, and 14b, respectively). [18F]12b and [18F]14b, with a longer fluoropegylated unit, that is, n = 3, showed faster brain washout at 30 min postinjection (0.42 and 1.57% dose/g) as compared to the shorter fluoropegylated chain ligands, that is, [18F]12a and [18F]14a (1.03 and 3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding signal due to Aβ plaques. These preliminary results suggest that the novel diphenylacetylenes may be potentially useful for imaging of Aβ plaques in the brain of patients with Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)2415-2423
Number of pages9
JournalJournal of Medicinal Chemistry
Volume50
Issue number10
DOIs
StatePublished - May 17 2007

ASJC Scopus subject areas

  • Organic Chemistry

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