11C-labeled stilbene derivatives as Aβ-aggregate-specific PET imaging agents for Alzheimer's disease

A series of stilbene derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of the stilbenes were successfully achieved by a simple Wadsworth-Emmons reaction between diethyl (4-nitrobenzyl)phosphonate and 4-methoxybenzaldehyde. 4-N,N-dimethylamino-4'-methyoxy and the corresponding 4-N-monomethylamino-, 4'-hydroxy stilbenes showed good binding affinities towards Abeta aggregates in vitro (K-i < 10 nM). The C-11 labeled 4-N-methylamino-4'-hydroxystilbene, [C-11]4, was prepared by C-11 methylation of 4-amino-4'-hydroxystilbene. The [C-11]4 displayed a moderate lipophilicity (log P = 2.36), and showed a very good brain penetration and washout from normal rat brain after an iv injection. In vitro autoradiography of transgenic AD mouse brain sections showed a high specific labeling of beta-amyloid plaques, whereas the control sections showed no binding. Taken together the data suggest that a relatively simple stilbene derivative, [C-11]4, N-[C-11]methylamino-4'-hydroxystilbene, may be useful as a positron emission tomography (PET) imaging agent for mapping A beta plaques in the brain of patients with Alzheimer's disease. (C) 2003 Elsevier Inc. All rights reserved.