Synthesis and evaluation of styrylpyran fluorophores for noninvasive detection of cerebral β-amyloid deposits

Abstract

The development of amyloid-specific fluorophores allows the visualization of cerebral β-amyloid deposits using optical imaging technology. In the present study, a series of smart styrylpyran fluorophores with compact donor–acceptor architecture were designed and evaluated for noninvasive detection of cerebral β-amyloid deposits. Spectral behavior of the fluorophores changed significantly (optical turn-on) upon binding to β-amyloid aggregates. Computational studies were conducted to correlate the experimental Kd values with calculated binding energies, speculating the relationship between fluorophore structure and β-amyloid affinity. In vivo studies demonstrated that PAD-2 could discriminate APP/PS1 transgenic mice from wild type controls, with specific labeling of cerebral β-amyloid deposits confirmed by ex vivo observation. Collectively, these styrylpyran fluorophores could provide a new scaffold for the development of optical imaging probes targeting cerebral β-amyloid deposits.