Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as Near-Infrared Probes for in Vivo Detection of Amyloid-β Deposits

被引：423

作者：

Ran, Chongzhao ^{[1
]}

Xu, Xiaoyin ^{[2
]}

Raymond, Scott B. ^{[3
]}

Ferrara, Brian J. ^{[3
]}

Neal, Krista ^{[3
]}

Bacskai, Brian J. ^{[3
]}

Medarova, Zdravka ^{[1
]}

Moore, Anna ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab,Dept Radio, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA

[2] Brigham & Womens Hosp, Dept Radiol, Opt Imaging Lab, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Boston, MA 02114 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 42期

关键词：

PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; MOUSE MODEL; TRANSGENIC MICE; CONTRAST AGENT; ZUR KENNTNIS; PLAQUES; BRAIN; PHOSPHORESCENCE; FLUORESCENCE;

D O I：

10.1021/ja9047043

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Amyloid-beta (A beta) deposits have been identified as key players in the progression of Alzheimer's disease (AD). Recent evidence indicates that the deposits probably precede and induce the neuronal atrophy. Therefore, methods that enable monitoring the pathology before clinical symptoms are observed would be beneficial for early AD detection. Here, we report the design, synthesis, and testing of a curcumin-derivatized near-infrared (NIR) probe, CRANAD-2. Upon interacting with A beta aggregates, CRANAD-2 undergoes a range of changes, which include a 70-fold fluorescence intensity increase, a 90 nm blue shift (from 805 to 715 nm), and a large increase in quantum yield. Moreover, this probe also shows a high affinity for A beta aggregates (K-d = 38.0 nM), a reasonable log P value (log P = 3), considerable stability in serum, and a weak interaction with albumin. After intravenous injection of this probe, 19-month-old Tg2576 mice exhibited significantly higher relative signal than that of the control mice over the same period of time. In summary, CRANAD-2 meets all the requirements for a NIR contrast agent for the detection of A beta plaques both in vitro and in vivo. Our data point toward the feasibility of monitoring the progress of the disease by NIR imaging with CRANAD-2. In addition, we believe that our probe could be potentially used as a tool for drug screening.

引用

页码：15257 / 15261

页数：5

共 39 条

[1] Curcumin suppresses the paclitaxel-induced nuclear factor-κB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice [J].