Radiolabeled pyridinyl analogues of dibenzylideneacetone as beta-amyloid imaging probes

In continuation of our investigation of the dibenzylideneacetone scaffold as A beta imaging probes, a series of derivatives containing pyridine rings with lower lipophilicity was synthesized and evaluated. Some of these probes displayed high affinities to A beta(1-42) aggregates, which ranged from 18.0 to 8.2 nM. The high and specific binding of the radiolabeled tracers was further confirmed by in vitro autoradiography on brain sections from AD patients and transgenic mouse. In biodistribution experiments, two F-18-labeled tracers [F-18]17a and [F-18]18 displayed high initial brain uptake ( 5.05 and 6.24% ID g(-1), respectively, at 2 min postinjection) and fast clearance from the brain with brain(2 min)/ brain(60 min) ratios of 6.08 and 8.00. These results demonstrate that the probes [F-18]17a and [F-18]18 with a dibenzylideneacetone structure containing pyridine rings have great strength in imaging A beta plaques in the brain.