Fluoro-substituted and ¹³C-labeled styrylbenzene derivatives for detecting brain amyloid plaques

Two styrylbenzene derivatives, (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4- hydroxy)styrylbenzene (FSB) and (E,E)-1-bromo-2,5-bis(3-hydroxycarbonyl-4- hydroxy)styrylbenzene-α,α′-¹³C₂ ([ ¹³C]BSB), were synthesized for use as a histochemical stain to detect amyloid plaques of Alzheimer's disease (AD) brain sections. An analysis of fluorescence spectra demonstrated that FSB shows approximately twofold fluorescence intensity relative to the conventional styrylbenzene derivative, (E,E)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB). Moreover, FSB was found to stain amyloid plaques and neurofibrillary tangles of AD brains with greater fluorescence intensity and a lower level of background signals compared to BSB. These finding indicate that FSB can be an excellent fluorescent compound to label human amyloid lesions with high sensitivity and specificity. Because of the possession of a nuclide with a quantized angular momentum, both FSB and [¹³C]BSB are also potential contrast agents for magnetic resonance imaging to locate AD pathologies in vivo.