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 Aβ1–42 aggregates (Ki = 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 Aβ 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.

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► (E)-5-styryl-2,2′-bithiophene derivatives showed high affinity to Aβ 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.