Novel quinoxaline derivatives for in vivo imaging of β-amyloid plaques in the brain

In a search for new probes to detect beta-amyloid plaques in the brain of patients with Alzheimer's disease (AD), we have synthesized and evaluated a series of quinoxaline derivatives containing a '6+6-6' ring system. These quinoxaline derivatives showed excellent affinity for A beta(1) (42) aggregates with K(i) values ranging from 2.6 to 10.7 nM. Autoradiography with sections of brain tissue from an animal model of AD mice (APP/PS1) and AD patients revealed that [(125)I]5 labeled beta-amyloid plaques specifically. In biodistribution experiments using normal mice, [(125)I]5 displayed high uptake (6.03% ID/g at 2 min) into and a moderately fast washout from the brain. Although additional refinements are needed to decrease the lipophilicity and improve the washout rate, the quinoxaline scaffold may be useful as a backbone structure to develop novel beta-amyloid imaging agents. (C) 2011 Elsevier Ltd. All rights reserved.