Radiolabeled pyridinyl analogues of dibenzylideneacetone as β-amyloid imaging probes

Abstract

In continuation of our investigation of the dibenzylideneacetone scaffold as Aβ imaging probes, a series of derivatives containing pyridine rings with lower lipophilicity was synthesized and evaluated. Some of these probes displayed high affinities to Aβ_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 ¹⁸F-labeled tracers [¹⁸F]17a and [¹⁸F]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 [¹⁸F]17a and [¹⁸F]18 with a dibenzylideneacetone structure containing pyridine rings have great strength in imaging Aβ plaques in the brain.