title: Polyfluorinated bis-styrylbenzenes as amyloid-β plaque binding ligands.
abstract: Detection of cerebral β-amyloid (Aβ) 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 Aβ imaging agents. To further explore their potency as (19)F MRI contrast agents we synthetized several novel fluorinated bis-styrylbenzenes and studied their fluorescent properties and amyloid-β binding characteristics. The compounds showed a high affinity for Aβ 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 (19)F NMR studies showed that these compounds as yet do not warrant further MRI studies due to the reduction of the (19)F signal in the environment of the brain.
authors.affiliation: Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands. Electronic address: r.j.a.nabuurs@lumc.nl.
authors.forename: Rob J A
authors.initials: RJ
authors.lastname: Nabuurs
authors.affiliation: Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands.
authors.forename: Varsha V
authors.initials: VV
authors.lastname: Kapoerchan
authors.affiliation: Radionucleotide Laboratory, Free University, Amsterdam, Netherlands.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxas
authors.affiliation: Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: de Jongh
authors.affiliation: Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: de Backer
authors.affiliation: Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Radionucleotide Laboratory, Free University, Amsterdam, Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands.
authors.forename: Hermen S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Overhand
authors.affiliation: Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Louise
authors.initials: L
authors.lastname: van der Weerd
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001554:Benzene / Q000737:chemistry* / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D013050:Spectrometry, Fluorescence
chemical_list: D016229:Amyloid beta-Peptides; D003287:Contrast Media; D005456:Fluorescent Dyes; D008024:Ligands; D005461:Fluorine; D001554:Benzene
keywords: Alzheimer’s disease; Amyloid β; Contrast agent; Fluorine; Imaging