Polyfluorinated bis-styrylbenzenes as amyloid-β plaque binding ligands

Area of Science:

• Neuroscience
• Radiochemistry
• Biochemistry

Background:

• Cerebral beta-amyloid (Aβ) detection is crucial for Alzheimer's disease (AD) diagnosis.
• Bis-styrylbenzenes are explored as potential Aβ imaging agents.

Purpose of the Study:

• To synthesize and evaluate novel fluorinated bis-styrylbenzenes as (19)F MRI contrast agents for Alzheimer's disease.
• To assess their fluorescent properties, Aβ binding affinity, and in vivo brain penetration.

Main Methods:

• Synthesis of novel fluorinated bis-styrylbenzenes.
• Fluorescence spectroscopy and amyloid-β binding assays.
• In vivo imaging in murine models and post-mortem (19)F NMR studies.

Main Results:

• Compounds exhibited high affinity for Aβ plaques in human and murine brain sections.
• Competitive binding indicated a distinct binding site compared to chrysamine G.
• Several compounds crossed the blood-brain barrier and labeled murine amyloid in vivo.
• Post-mortem (19)F NMR revealed signal reduction in the brain environment, hindering MRI potential.

Conclusions:

• Fluorinated bis-styrylbenzenes demonstrate promising Aβ plaque binding and in vivo brain penetration for Alzheimer's disease imaging.
• Signal attenuation in vivo currently precludes their use as (19)F MRI contrast agents.