title: 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 inflammatory mediators are normally maintained at very low levels due to their strong ability to induce a biological response. The production, diffusion, and decomposition of such mediators are spatio-temporally regulated. Therefore, 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 inflammatory diseases; however, the lack of effective imaging technology has made it difficult 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 fill this technical gap by developing highly sensitive imaging mass spectrometry (IMS) technologies. To date, we have established two key techniques toward this goal, including (i) a sample preparation procedure that has eliminated the problem of the postmortem degradation of labile metabolites, and (ii) on-tissue derivatization of metabolites, which can enhance analyte ionization efficiency. Here, we review recent progress in the development of these technologies as well as how the highly sensitive IMS technique has contributed to increasing understanding of the biochemical basis of disease mechanisms, discovery of new diagnostic markers, and development of new therapies.
authors.affiliation: Department of Biochemistry, Keio University School of Medicine; JST Precursory Research for Embryonic Science and Technology (PRESTO) Project.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Biochemistry, Keio University School of Medicine.
authors.forename: Kurara
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Biochemistry, Keio University School of Medicine; Japan Science and Technology Agency, Exploratory Research for Advanced Technology (ERATO)  Suematsu Gas Biology Project.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
keywords: imaging mass spectrometry; on tissue derivatization; postmortem degradation of metabolites
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18120-5
references.pmid: 18697929
references.citation: J Microw Power. 1977 Dec;12(4):273-86
references.pmid: 210282
references.citation: Nat Med. 2001 Apr;7(4):493-6
references.pmid: 11283679
references.citation: FEBS J. 2014 Oct;281(20):4672-90
references.pmid: 25143155
references.citation: Anal Bioanal Chem. 2012 Jun;403(7):1851-61
references.pmid: 22526660
references.citation: Antioxid Redox Signal. 2010 Oct;13(8):1157-67
references.pmid: 20486758
references.citation: Anal Chem. 2011 Jan 1;83(1):207-15
references.pmid: 21142140
references.citation: Anal Chem. 2009 Jul 1;81(13):5557-60
references.pmid: 19514699
references.citation: J Microw Power. 1978 Mar;13(1):53-7
references.pmid: 361966
references.citation: Anal Chem. 2007 Mar 15;79(6):2199-206
references.pmid: 17302385
references.citation: Neuron. 2014 Nov 19;84(4):697-707
references.pmid: 25453841
references.citation: Anal Bioanal Chem. 2011 Jun;400(7):1933-43
references.pmid: 21461619
references.citation: Clin Chem. 2003 Jul;49(7):1041-4
references.pmid: 12816898
references.citation: J Cereb Blood Flow Metab. 2015 May;35(5):794-805
references.pmid: 25586144
references.citation: Mol Cell Proteomics. 2009 Sep;8(9):2023-33
references.pmid: 19451175
references.citation: J Neuroimmune Pharmacol. 2010 Mar;5(1):31-43
references.pmid: 19513855
references.citation: Proteomics. 2014 Apr;14(7-8):810-9
references.pmid: 23818158
references.citation: Anal Chem. 2007 Nov 1;79(21):8098-106
references.pmid: 17900146
references.citation: J Mass Spectrom. 2011 Aug;46(8):840-6
references.pmid: 21834023
references.citation: Mol Cancer Res. 2013 Sep;11(9):973-85
references.pmid: 23741060
references.citation: Sci Rep. 2014 Nov 20;4:7130
references.pmid: 25410733
references.citation: Anal Chem. 2009 Apr 15;81(8):2823-31
references.pmid: 19296690
references.citation: Proteomics. 2014 Apr;14(7-8):829-38
references.pmid: 23970501
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13811-6
references.pmid: 22869730
references.citation: Neuroscience. 1992 Nov;51(1):55-64
references.pmid: 1465186
references.citation: J Am Soc Mass Spectrom. 2015 Jun;26(6):934-9
references.pmid: 25821050
references.citation: J Lipid Res. 2009 Sep;50(9):1776-88
references.pmid: 19417221
references.citation: Anal Chem. 1999 Oct 1;71(19):4160-5
references.pmid: 10517141
references.citation: Cell Death Dis. 2013 Nov 14;4:e919
references.pmid: 24232095
references.citation: Nat Methods. 2007 Oct;4(10):828-33
references.pmid: 17901873
references.citation: Mass Spectrom Rev. 2007 Jul-Aug;26(4):606-43
references.pmid: 17471576
references.citation: Neuroscience. 2010 Oct 27;170(3):858-64
references.pmid: 20670678
references.citation: Anal Biochem. 1996 Jan 1;233(1):94-9
references.pmid: 8789152
references.citation: Anal Chem. 2006 Sep 15;78(18):6448-56
references.pmid: 16970320
references.citation: Biochem J. 1929;23(5):1126-36
references.pmid: 16744282
references.citation: J Immunol. 2013 Mar 1;190(5):2036-48
references.pmid: 23365076
references.citation: Anal Chem. 2008 Jun 15;80(12):4761-6
references.pmid: 18476721
references.citation: PLoS One. 2011 Mar 22;6(3):e17952
references.pmid: 21445350
references.citation: Nature. 2012 Jan 15;481(7382):516-9
references.pmid: 22246326
references.citation: Chem Rev. 2011 Oct 12;111(10):6491-512
references.pmid: 21942646
references.citation: Anal Bioanal Chem. 2012 Jun;403(7):1873-84
references.pmid: 22415026
references.citation: J Pharm Pharmacol. 1978 Jun;30(6):371-4
references.pmid: 26769
references.citation: Respir Physiol Neurobiol. 2012 Nov 15;184(2):139-48
references.pmid: 22516267
references.citation: J Neurosci Methods. 1996 Feb;64(2):151-6
references.pmid: 8699875
references.citation: J Pharmacol Toxicol Methods. 2007 Mar-Apr;55(2):193-200
references.pmid: 16919485
references.citation: Anal Chem. 2008 Jul 15;80(14):5648-53
references.pmid: 18564854
references.citation: Life Sci. 1981 Aug 17;29(7):643-53
references.pmid: 6116141
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 24;109 (4):1293-8
references.pmid: 22232681
references.citation: J Neurosci. 2011 Aug 3;31(31):11411-20
references.pmid: 21813701
references.citation: Anal Chem. 2013 Dec 3;85(23):11576-84
references.pmid: 24134553