Carbon-11 labeled stilbene derivatives from natural products for the imaging of Aβ plaques in the brain

摘要

Four stilbene derivatives from natural products were screened as novel β-amyloid (Aβ) imaging ligands. In vitro binding assay showed that the methylated ligand, (E)-1-methoxy-4-styrylbenzene (8) displayed high binding affinity to Aβ(1-42) aggregates (K_i = 19.5 nM). Moreover, the ~(11)C-labeled ligand, [~(11)C]8 was prepared through an β- methylation reaction using [~(11)C]CH_3OTf. In vitro autoradiography with sections of transgenic mouse brain also confirmed the high and specific binding of [~(11)C]8 to Aβ plaques. In vivo biodistribution experiments in normal mice indicated that [~(11)C]8 displayed high initial uptake (9.41 ± 0.51% ID/g at5min post-injection) into and rapid washout fromthe brain, with a brain_(5 min)/brain_(30 min) ratio of 6.63. These preliminary results suggest that [~(11)C]8 may be served as a novel Aβ imaging probe for PET.