Polyfluorinated bis-styrylbenzenes as amyloid-beta plaque binding ligands

Publication Type:

Journal Article

Source:

Bioorganic & medicinal chemistry, Volume 22, Issue 8, pp. 2469–2481 (2014)

ISBN:

1464-3391 (Electronic)09

DOI Name (links to online publication)

10.1016/j.bmc.2014.02.054

Abstract:

Detection of cerebral beta-amyloid (Abeta) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Abeta imaging agents. To further explore their potency as 19F MRI contrast agents we synthetized several novel fluorinated bis-styrylbenzenes and studied their fluorescent properties and amyloid-beta binding characteristics. The compounds showed a high affinity for Abeta plaques on murine and human brain sections. Interestingly, competitive binding experiments demonstrated that they bound to a different binding site than chrysamine G. Despite their high logP values, many bis-styrylbenzenes were able to enter the brain and label murine amyloid in vivo. Unfortunately initial post-mortem 19F NMR studies showed that these compounds as yet do not warrant further MRI studies due to the reduction of the 19F signal in the environment of the brain.

14/04/2014