Synthesis and characterization of styrylchromone derivatives as β-amyloid imaging agents

Abstract Several promising agents have been synthesized and evaluated for in vivo imaging probes of β-amyloid plaques in Alzheimer’s disease (AD) brain. Recently, we have developed flavone derivatives, which possess the basic structure of the 2-phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to further develop novel tracers, we synthesized and evaluated a series of 2-styrylchromone derivatives, which replace the 2-phenyl substituent of flavone backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives were designed and synthesized. The binding affinities for amyloid plaques were assessed by in vitro binding assay using pre-formed synthetic Aβ(1–40) aggregates. The new series of styrylchromone derivatives showed high binding affinity to Aβ aggregates at the K d values of 32.0, 17.5 and 8.7 nM for [ 125 I] 6 , [ 125 I] 9 , and [ 125 I] 12 , respectively. In biodistribution studies using normal mice, [ 125 I] 6 and [ 125 I] 9 examined in normal mice displayed high brain uptakes with 4.9 and 2.8%ID/g at 2 min post injection. The radioactivity washed out from the brain rapidly (1.6 and 1.0%ID/g at 60 min post injection for [ 125 I] 6 and [ 125 I] 9 , respectively). But [ 125 I] 12 did not show marked brain uptake, and the washout rate from the brain was relatively slow throughout the time course (1.1 and 1.4%ID/g at 2 and 30 min post injection, respectively). Although additional modifications are necessary to improve the brain uptake and rapid clearance of non-specifically bound radiotracer, the styrylchromone backbone may be useful as a backbone structure to develop novel β-amyloid imaging agents.