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Design, Synthesis, and Imaging of an Activatable Photoacoustic Probe
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2010-08-18 , DOI: 10.1021/ja104000a
Jelena Levi 1 , Sri Rajasekhar Kothapalli , Te-Jen Ma , Keith Hartman , Butrus T Khuri-Yakub , Sanjiv Sam Gambhir
Affiliation  

Photoacoustic tomography is a rapidly growing imaging modality that can provide images of high spatial resolution and high contrast at depths up to 5 cm. We report here the design, synthesis, and evaluation of an activatable probe that shows great promise for enabling detection of the cleaved probe in the presence of high levels of nonactivated, uncleaved probe, a difficult task to attain in absorbance-based modality. Before the cleavage by its target, proteolytic enzyme MMP-2, the probe, an activatable cell-penetrating peptide, Ceeee[Ahx]PLGLAGrrrrrK, labeled with two chromophores, BHQ3 and Alexa750, shows photoacoustic signals of similar intensity at the two wavelengths corresponding to the absorption maxima of the chromophores, 675 and 750 nm. Subtraction of the images taken at these two wavelengths makes the probe effectively photoacoustically silent, as the signals at these two wavelengths essentially cancel out. After the cleavage, the dye associated with the cell-penetrating part of the probe, BHQ3, accumulates in the cells, while the other dye diffuses away, resulting in photoacoustic signal seen at only one of the wavelengths, 675 nm. Subtraction of the photoacoustic images at two wavelengths reveals the location of the cleaved (activated) probe. In the search for the chromophores that are best suited for photoacoustic imaging, we have investigated the photoacoustic signals of five chromophores absorbing in the near-infrared region. We have found that the photoacoustic signal did not correlate with the absorbance and fluorescence of the molecules, as the highest photoacoustic signal arose from the least absorbing quenchers, BHQ3 and QXL 680.

中文翻译:


可激活光声探针的设计、合成和成像



光声断层扫描是一种快速发展的成像方式,可以在深度达 5 厘米的情况下提供高空间分辨率和高对比度的图像。我们在此报告了一种可激活探针的设计、合成和评估,该探针显示出在存在高水平未激活、未切割探针的情况下检测切割探针的巨大前景,这在基于吸光度的模式中是一项艰巨的任务。在被其目标蛋白水解酶 MMP-2 裂解之前,探针是一种可激活的细胞穿透肽 Ceeee[Ahx]PLGLLAGrrrrrK,用两个发色团 BHQ3 和 Alexa750 标记,在对应于发色团的最大吸收,675 和 750 nm。减去在这两个波长处拍摄的图像使探头实际上实现光声静音,因为这两个波长处的信号基本上相互抵消。裂解后,与探针 BHQ3 的细胞穿透部分相关的染料在细胞中积聚,而另一种染料则扩散开,导致仅在一个波长(675 nm)处看到光声信号。两个波长的光声图像相减揭示了裂解(激活)探针的位置。在寻找最适合光声成像的生色团的过程中,我们研究了五种生色团在近红外区域吸收的光声信号。我们发现光声信号与分子的吸光度和荧光不相关,因为最高的光声信号来自吸收最少的猝灭剂 BHQ3 和 QXL 680。
更新日期:2010-08-18
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