Structure−Activity Relationship of Imidazo[1,2-a]pyridines as Ligands for Detecting β-Amyloid Plaques in the Brain

摘要: A series of novel beta-amyloid (A beta) aggregate-specific ligands, 2-(4'-dimethylaminophenyl)-6-iodoimidazo[1,2-a]pyridine, 16(IMPY), and its related derivatives were prepared. An in vitro binding study with preformed beta aggregates showed that 16(IMPY) bromo derivative competed 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [125I]7(TZDM), a known ligand for aggregates, high affinities (K(i) = 15 10 nM, respectively). In autoradiography brain sections transgenic mouse (Tg2576) [125I]16(IMPY) displayed selective to amyloid-like structures, comparable observed by staining thioflavin-S visualized under fluorescence. vivo biodistribution after an intravenous injection normal mice initial uptake fast washout, indicating low background activity associated this iodinated ligand. Taken together, the data suggests [123I]16(IMPY) may be useful imaging patients Alzheimer's disease.