Structure-activity relationship of imidazo[1,2-a]pyridines as ligands for detecting β-amyloid plaques in the brain

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