11C-labeled stilbene derivatives as A-aggregate-specific PET imaging agents for Alzheimerfs 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 A aggregates in vitro (Ki < 10 nM). The 11C labeled 4-N-methylamino-4'-hydroxystilbene, [11C]4, was prepared by 11C methylation of 4-amino-4'-hydroxystilbene. The [11C]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 -amyloid plaques, whereas the control sections showed no binding. Taken together the data suggest that a relatively simple stilbene derivative, [11C]4,N-[11C]methylamino-4'hydroxystilbene, may be useful as a positron emission tomography (PET) imaging agent for mapping A plaques in the brain of patients with Alzheimer's disease.