Khatib-Shahidi Sheerin, Andersson Malin, Herman Jennifer L, Gillespie Todd A, Caprioli Richard M
Mass Spectrometry Research Center, Departments of Chemistry and Biochemistry, Vanderbilt University, 465 21st Avenue S, Suite 9160 MRB III, Nashville, Tennessee 37221, USA.
Anal Chem. 2006 Sep 15;78(18):6448-56. doi: 10.1021/ac060788p.
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.
利用基质辅助激光解吸/电离（MALDI）技术的成像质谱（IMS）能够提供切除器官或动物全身切片的分子离体视图，从而实现对内源和外源化合物进行具有空间分辨率和分子特异性的无标记追踪。在给药后的不同时间点，可以同时检测药物在全身组织切片中的分布以及首次检测到的个体代谢物分布。对给予8 mg/kg奥氮平的大鼠组织进行的IMS分析揭示了药物和代谢物的时间分布，这与之前的定量全身放射自显影研究相关。全身MALDI IMS进一步扩展到检测全身矢状组织切片中器官的蛋白质。这项技术将极大地有助于推进新型治疗药物的分析，并可能提供对治疗和毒理学过程更深入的见解，在分子水平揭示通常与药物给药相关的疗效或副作用的原因。
