MALDI mass spectrometric imaging of biological tissue sections

MALDI mass spectrometric imaging of biological tissue sections
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DOI:
10.1016/j.mad.2004.09.032
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发表时间:
2005-01-01
影响因子:
5.3
通讯作者:
Stoeckli, M
Stoeckli, M
中科院分区:
医学3区
文献类型:
--
作者:
Rohner, TC;Staab, D;Stoeckli, M

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在生物医学研究中,发现新的生物标志物和新药需要高灵敏度的分析技术以及更高的通量。通过成像特定组织的组分分布来定位或跟踪生物体在分子水平上的变化的可能性对于解开生物化学途径和开发新的治疗方法和药物是至关重要的。已建立的分子成像技术如MRI和PET已经被广泛使用,然而它们需要分子探针来报告感兴趣的分析物的存在,从而排除了对不同生物分子的同时探索。基质辅助激光解吸/电离质谱成像(MALDI MSI)充分利用了质谱仪器的NO灵敏度,也利用了后者同时检测多种化合物的能力。几乎不考虑它们的性质和质量。为了执行MALDI MSL,将生物组织的切片引入MALDI MS仪器中,其中MALDI源的UV脉冲激光用于在选定区域上进行光栅扫描,同时在每个图像点处获取烧蚀离子的质谱。从这个光谱阵列中,可以基于所选择的质量生成数百个分析物特异性图像。MALDI MSI可用于跟踪生物标志物,如肽或蛋白质,也可用于绘制药物/组织相互作用。在这篇论文中。将给出MSI的可能性的概述。作为一个例子,将显示用于研究阿尔茨海默病(AD)的脑组织切片上的MSI。将淀粉样肽作为一种新的药物先导物优化方法的映射。目标识别感谢NISI将被介绍,最后一部分将致力于分子扫描仪的方法。其通过在一步过程中结合组织印迹和消化来获得高质量范围。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
In biomedical research, the discovery of new biomarkers and new drugs demands analytical techniques with high sensitivity together with increased throughput. The possibility to localize or to follow changes in organisms at the molecular level by imaging component distributions of specific tissues, is of prime importance to unravel biochemical pathways and develop new treatments and drugs. Established molecular imaging techniques such as MRI and PET are already widely used,however their need for molecular probes to report the presence of the analytes of interest precludes the simultaneous exploration of different biomolecules. Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) takes full advantage of the NO sensitivity of mass spectrometry instrumentation but also of the ability of the latter to simultaneously detect a wide range of compounds. almost regardless from their nature and mass. To perform MALDI MSL sections of biological tissues are introduced in an MALDI MS instrument, where the UV pulsed laser of the MALDI source is used to raster over a selected area while acquiring mass spectra of the ablated ions at every image point. From this array of spectra, hundreds of analyte-specific images can be generated based on the selected masses. MALDI MSI can he used to track biomarkers such as peptides or proteins but also to map drug/tissue interactions. In this paper. an overview of the possibilities of MSI will be given. As an example, MSI on brain tissue sections for the study of Alzheimer's disease (AD) will be shown. Mapping of amyloid peptides as a new approach for drug lead optimization will be presented. Target identification thanks to NISI will be introduced and the last part will be dedicated to the molecular scanner approach. which gives access to high-mass range by combining tissue blotting and digestion in a one-step process. (C) 2004 Elsevier Ireland Ltd. All rights reserved.