Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry
Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry
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DOI：
10.1021/ac060788p
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发表时间：
2006-09-15
影响因子：
7.4
通讯作者：
Caprioli, Richard M.
中科院分区：
文献类型：
--
作者：
Khatib-Shahidi, Sheerin;Andersson, Malin;Caprioli, Richard M.
利用基质辅助激光解吸/电离（MALDI）技术的成像质谱（IMS）可以提供从动物切除的器官或全身切片的分子离体视图，使得能够以空间分辨率和分子特异性对内源性和外源性化合物进行无标记追踪。药物分布和第一次，在全身组织切片中的单个代谢物分布可以在给药后的不同时间点同时检测。对8 mg/kg奥氮平给药大鼠的组织进行IMS分析，发现药物和代谢物的时间分布与先前的定量全身放射自显影研究相关。全身MALDI IMS进一步扩展到检测来自全身矢状组织切片中存在的器官的蛋白质。这项技术将大大有助于推进新疗法的分析，并可能提供更深入的了解治疗和毒理学过程，揭示在分子水平上的疗效或副作用的原因往往与药物管理。
Imaging mass spectrometry (IMS) that utilizes matrix-assisted laser desorption/ionization (MALDI) technology can provide a molecular ex vivo view of resected organs or whole-body sections from an animal, making possible the label-free tracking of both endogenous and exogenous compounds with spatial resolution and molecular specificity. Drug distribution and, for the first time, individual metabolite distributions within whole-body tissue sections can be detected simultaneously at various time points following drug administration. IMS analysis of tissues from 8 mg/kg olanzapine dosed rats revealed temporal distribution of the drug and metabolites that correlate to previous quantitative whole-body autoradiography studies. Whole-body MALDI IMS is further extended to detecting proteins from organs present in a whole-body sagittal tissue section. This technology will significantly help advance the analysis of novel therapeutics and may provide deeper insight into therapeutic and toxicological processes, revealing at the molecular level the cause of efficacy or side effects often associated with drug administration.