title: In vivo detection of cerebral amyloid fibrils with smart dicynomethylene-4H-pyran-based fluorescence probe.
abstract: In vivo detection of cerebral β-amyloid fibrils may facilitate the monitoring of β-amyloidosis in the brain and effectiveness of antiamyloid therapies. Thioflavin T (ThT) is a widely used dye for the spectroscopic determination of β-amyloid fibrils, but its ability to detect cerebral β-amyloid fibrils in vivo is limited due to the charged molecule. To this end, a smart dicynomethylene-4H-pyran (DCM) fluorophore, namely, (E)-2-(2-(4-(dimethylamino)styryl)-6-methyl-4H-pyran-4-ylidene) malononitrile (PAD-1), was evaluated for in vivo fluorescence imaging of cerebral β-amyloid fibrils. PAD-1 rapidly entered the brain with high initial brain uptake after intravenous injection, which is highly desirable for in vivo detection of β-amyloid fibrils. PAD-1 displayed a turn-on effect, showing significant enhancement in fluorescence when bound to the aggregated β-amyloid fibrils. It also showed specific labeling of β-amyloid deposits in APP/PS1 transgenic mouse brains. Thus, PAD-1 proved to be a valuable alternative to ThT for cerebral β-amyloid detection and may enable quantitative imaging in vivo.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Yan
authors: Y
authors: Cheng
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Biyue
authors: B
authors: Zhu
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Yue
authors: Y
authors: Deng
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Zhirong
authors: Z
authors: Zhang
mesh_terms: D000682:Amyloid / Q000032:analysis* / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015394:Molecular Structure; D009570:Nitriles / Q000032:analysis / Q000737:chemistry*; D011714:Pyrans / Q000032:analysis / Q000737:chemistry*
chemical_list: C000602503:2-(2-(4-(dimethylamino)styryl)-6-methyl-4H-pyran-4-ylidene)malononitrile; D000682:Amyloid; D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D009570:Nitriles; D011714:Pyrans