Diphenylpropynone derivatives as probes for imaging beta-amyloid plaques in Alzheimer's brains

A new series of diphenylpropynone (DPP) derivatives for use in vivo to image beta-amyloid (A beta) plaques in the brain of patients with Alzheimer's disease (AD) were synthesized and characterized. Binding experiments in vitro revealed high affinity for A beta (1-42) aggregates at a K(i) value ranging from 6 to 326 nM. Furthermore, specific labeling of plaques was observed in sections of brain tissue from Tg2576 transgenic mice stained using one of the compounds, 1. In biodistribution experiments with normal mice, [(125)I]1displayed moderate uptake (1.55% ID/g at 2 min) and clearance from the brain with time (0.76 ID/g at 60 min). Taken together, DPP can serve as a new molecular scaffold for developing novel A beta imaging agents by introducing appropriate substituted groups. (C) 2010 Elsevier Ltd. All rights reserved.