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

Abstract

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 Aβ aggregates in vitro (K i < 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 β-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 Aβ plaques in the brain of patients with Alzheimer’s disease.