Synthesis and Evaluation of ¹²⁵I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes

In continuation of the investigation on the bithiophene structure as potential Aβ probes, two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβ plaques. In vitro fluorescence staining indicated that they could stain Aβ plaques in the brain sections of AD model mice specifically, in vitro binding assay further confirmed that they displayed high binding affinities to Aβ aggregates (K_i=2.33 nM and 0.88 nM). One radio-iodinated probe, ¹²⁵I labeleled chalcone derivatives was obtained via iododestannylation reaction with high radiochemical yield and purity (>99%). Moreover, the ¹²⁵I-labeling compound displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background, and the specific labeling could be confirmed by thioflavin-S staining. In vivo biodistribution in normal mice indicated that the ¹²⁵I labeling compound exhibited low initial brain uptake (1.19%ID/g at 2 min) and rapid clearance. These preliminary results suggest that ¹²⁵I labeling compound may serve as novel Aβ imaging probe, although further modifications are needed to improve initial brain uptake.