Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues

Abstract

In vivo concentrations of cellular signaling mediators such as in mediators are normally maintained at very low levels due to their strong ability to induce a biological response. e production, di and decomposition of such mediators are spatio-temporally regulated. erefore, in order to understand biochemical basis of disease progression and develop new therapeutic strategies, it is important to understand the spatiotemporal dynamics of the signaling mediators in vivo, during the progression of disorders, e.g., chronic in diseases; however, the lack of e imaging technology has made it di to determine their localizations in vivo. Such characterization requires technical breakthroughs, including molecular imaging methods that are sensitive enough to detect low levels of metabolites in the heterogeneous tissue regions in diseased organs. We and other groups have attempted to ll this technical gap by developing highly sensitive imaging mass spectrometry (IMS) technologies. To date, we have estab-lished two key techniques toward this goal, including (i) a sample preparation procedure that has elimi-nated the problem of the postmortem degradation of labile metabolites, and (ii) on-tissue derivatization of metabolites, which can enhance analyte ionization e Here, we review recent progress in the devel-opment of these technologies as well as how the highly sensitive IMS technique has contributed to increas-ing understanding of the biochemical basis of disease mechanisms, discovery of new diagnostic markers, and development of new therapies. Please cite this article as: Mass Spectrom (Tokyo) 2015; 4(1): A0040