Styryl-based compounds as potential in vivo imaging agents for beta-amyloid plaques.
A group of styryl-based neutral compounds has been synthesized in this study for potential use as in vivo imaging agents for beta-amyloid plaques. Of 56 candidates, 14 compounds were found to label beta-amyloid plaques well on Alzheimer's disease (AD) human brain sections in vitro. The binding affinity to beta-amyloid fibrils was then determined by measuring the change in fluorescence intensity. Interestingly, we found that a class of quinaldine-styryl scaffold compounds displays specific binding to beta-amyloid fibrils. A representative compound, STB-8, was used in ex vivo and in vivo imaging experiments on an AD transgenic mouse model and demonstrated excellent blood-brain barrier (BBB) permeability and specific staining of the AD beta-amyloid plaques.
Li
Qian
Q
Department of Chemistry, New York University, School of Medicine, New York, NY 11219, USA.
Min
Jaeki
J
Ahn
Young-Hoon
YH
Namm
Joshua
J
Kim
Eun Min
EM
Lui
Rowena
R
Kim
Hye Yun
HY
Ji
Yong
Y
Wu
Hueizhi
H
Wisniewski
Thomas
T
Chang
Young-Tae
YT
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D001812:Blood-Brain Barrier; D003287:Contrast Media / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D008956:Models, Chemical; D010539:Permeability; D058225:Plaque, Amyloid / Q000473:pathology*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence / Q000379:methods
D016229:Amyloid beta-Peptides; D003287:Contrast Media