Polyfluorinated bis-styrylbenzenes as amyloid-β plaque binding ligands |
| |
Institution: | 1. Department of Radiology CS2, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands;2. Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands;3. Radionucleotide Laboratory, Free University, Amsterdam, Netherlands;4. Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Netherlands;5. Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands;1. Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, 128 40 Prague 2, Czech Republic;2. J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i, Dolejškova 3, 182 23 Prague 8, Czech Republic;1. Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation;2. N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation;1. ICBMS UMR 5246 CNRS, Institute of Chemistry and Biochemistry, Université Lyon 1, Centre National de la Recherche Scientifique, 69622 Villeurbanne, France;2. École Supérieure de Chimie Physique Électronique de Lyon, 69616 Villeurbanne, France;3. CERMEP – In Vivo Imaging, Groupement Hospitalier Est, 69003 Lyon, France |
| |
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 19F 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 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. |
| |
Keywords: | Amyloid β Fluorine Imaging Alzheimer’s disease Contrast agent |
本文献已被 ScienceDirect 等数据库收录! |
|