Smart optical probes for near-infrared fluorescence imaging of Alzheimer's disease pathology

Purpose Near-infrared fluorescent probes for amyloid-beta (A beta) are an exciting option for molecular imaging in Alzheimer's disease research and may translate to clinical diagnostics. However, A beta-targeted optical probes often suffer from poor specificity and slow clearance from the brain. We are designing smart optical probes that emit characteristic fluorescence signal only when bound to A beta. Methods We synthesized a family of dyes and tested A beta-binding sensitivity with fluorescence spectroscopy and tissue-staining. Results Select compounds exhibited A beta-dependent changes in fluorescence quantum yield, lifetime, and emission spectra that may be imaged microscopically or in vivo using new lifetime and spectral fluorescence imaging techniques. Conclusion Smart optical probes that turn on when bound to A beta will improve amyloid detection and may enable quantitative molecular imaging in vivo.