Novel ( E)-5-styryl-2,2′-bithiophene derivatives as ligands for β-amyloid plaques

In continuation of our investigation on the bithiophene structure as potential β-amyloid probes, a series of ( E)-5-styryl-2,2′-bithiophene (SBTP) derivatives was designed and synthesized. In vitro binding showed that all of them displayed high binding affinities to A β 1–42 aggregates ( K i = 0.10–41.05 nM). Moreover, two radio-iodinated probes, [ 125I]-( E)-5-(4-iodostyryl)-2,2′-bithiophene ([ 125I] 8) and [ 125I]-( E)-5-iodo-5′-(4-methoxystyryl)-2,2′-bithiophene ([ 125I] 31) were prepared. Both of them displayed specific labeling of A β plaques in the brain sections of AD model mice with low background. In vivo biodistribution in normal mice indicated that [ 125I] 8 exhibited high initial brain uptake (2.11% ID/g at 2 min) and rapid clearance (0.41% ID/g at 30 min). These preliminary results suggest that SBTP derivatives may be served as novel β-amyloid imaging probes. [Display omitted] ► ( E)-5-styryl-2,2′-bithiophene derivatives showed high affinity to A β aggregates. ► High tolerance for steric bulk at para position of the phenyl ring was found. ► 125I labeled probes showed excellent plaque labeling in the brain of AD model mice. ► One of the tracers showed high uptake and fast washout from the normal mice brain.