Homoisoflavonoids as potential imaging agents for β-amyloid plaques in Alzheimer's disease

• A series of homoisoflavonoids were readily prepared.
• Some compounds demonstrated high binding affinities to Aβ aggregates.
• High initial brain uptake and rapid clearance from the normal mice brain.
• Novel potential imaging agents for Aβ plaques in AD brain.

A series of homoisoflavonoids [(E)-3-benzylidenechroman-4-ones, 3a–l] as novel potential diagnostic imaging agents targeting β-amyloid (Aβ) plaques in Alzheimer's disease (AD) were synthesized and evaluated. In vitro binding studies using Aβ1–40 aggregates with [125I]IMPY as the reference ligand showed that these compounds demonstrated high to low binding affinities at the Ki values ranged from 9.10 to 432.03 nM, depending on the substitution of the phenyl ring. Fluorescent staining in vitro indicated that one compound with a N,N-dimethylamino group intensely stained Aβ plaques within brain sections of postmortem AD patients. Biodistribution studies in normal mice after i.v. injection of the radioiodinated homoisoflavonoid displayed good initial brain uptake (2.61% ID/g at 2 min postinjection) and rapid clearance from the brain (0.18% ID/g at 60 min), which is desirable for amyloid imaging agents. The results strongly suggest that these derivatives are worthy of further study and may be useful amyloid imaging agents for early detection of amyloid plaques in the brain of AD.

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