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Mass Spectrometry-Based Tissue Imaging of Small Molecules

  • Carly N. Ferguson
  • Joseph W. M. Fowler
  • Jonathan F. Waxer
  • Richard A. Gatti
  • Joseph A. LooEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1140)

Abstract

Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques, and provides accurate, histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from mass spectrometry imaging laboratories around the globe.

Keywords

Mass spectrometry tissue imaging Small molecules Lipids Drug compounds Nanoparticles 

Notes

Acknowledgments

This work was supported by the Ruth L. Kirschstein National Research Service Award (Grant GM007185, UCLA Cellular and Molecular Biology Training Grant, for C.N.F.) and the US National Institutes of Health Shared Instrumentation Program (Grant S10 RR025600 to J.A.L.).

References

  1. 1.
    Mcdonnell, L. A., & Heeren, R. M. (2007). Imaging mass spectrometry. Mass Spectrometry Reviews, 26, 606–643.PubMedGoogle Scholar
  2. 2.
    Reyzer, M., & Caprioli, R. (2011). Imaging mass spectrometry. In J. Banoub (Ed.), Detection of biological agents for the prevention of bioterrorism. The Netherlands: Springer.Google Scholar
  3. 3.
    Coons, A. H., Creech, H. J., Jones, R. N., & Berliner, E. (1942). The demonstration of pneumococcal antigen in tissues by the use of fluorescent antibody. Journal of Immunology, 45, 159–170.Google Scholar
  4. 4.
    Andersson, M., Groseclose, M. R., Deutch, A. Y., & Caprioli, R. M. (2008). Imaging mass spectrometry of proteins and peptides: 3D Volume reconstruction. Nature Methods, 5, 101–108.PubMedGoogle Scholar
  5. 5.
    Sanchez-Carbayo, M. (2006). Antibody arrays: Technical considerations and clinical applications in cancer. Clinical Chemistry, 52, 1651–1659.PubMedGoogle Scholar
  6. 6.
    Lazova, R., Seeley, E. H., Keenan, M., Gueorguieva, R., & Caprioli, R. M. (2012). Imaging mass spectrometry—A new and promising method to differentiate Spitz nevi from Spitzoid malignant melanomas. The American Journal of Dermatopathology, 34, 82–90.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Fahy, E., Subramaniam, S., Brown, H. A., Glass, C. K., Merrill, A. H., Murphy, R. C., et al. (2005). A comprehensive classification system for lipids. Journal of Lipid Research, 46, 839–862.PubMedGoogle Scholar
  8. 8.
    Murphy, R. C., Hankin, J. A., & Barkley, R. M. (2009). Imaging of lipid species by MALDI mass spectrometry. Journal of Lipid Research, 50, S317–S322.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Bulley, N. R., Fattori, M., Meisen, A., & Moyls, L. (1984). Supercritical fluid extraction of vegetable oil seeds. Journal of the American Oil Chemists’ Society, 61, 1362–1365.Google Scholar
  10. 10.
    Conte, E., Milani, R., Morali, G., & Abballe, F. (1997). Comparison between accelerated solvent extraction and traditional extraction methods for the analysis of the herbicide diflufenican in soil. Journal of Chromatography A, 765, 121–125.Google Scholar
  11. 11.
    García-Ayuso, L. E., Velasco, J., Dobarganes, M. C., & Luque De Castro, M. D. (2000). Determination of the oil content of seeds by focused microwave-assisted Soxhlet extraction. Chromatographia, 52, 103–108.Google Scholar
  12. 12.
    Taylor, S., King, J., & List, G. (1993). Determination of oil content in oilseeds by analytical supercritical fluid extraction. Journal of the American Oil Chemists’ Society, 70, 437–439.Google Scholar
  13. 13.
    Wenk, M. R. (2005). The emerging field of lipidomics. Nature Reviews. Drug Discovery, 4, 594–610.PubMedGoogle Scholar
  14. 14.
    Schultz, C., Neef, A. B., Gadella, T. W., & Goedhart, J. (2010). Imaging lipids in living cells. Cold Spring Harbor Protocols, 2010, Pdb.Top83.PubMedGoogle Scholar
  15. 15.
    Ellis, S. R., Brown, S. H., In Het Panhuis, M., Blanksby, S. J., & Mitchell, T. W. (2013). Surface analysis of lipids by mass spectrometry: More than just imaging. Progress in Lipid Research, 52, 329–353.PubMedGoogle Scholar
  16. 16.
    Zemski Berry, K. A., Hankin, J. A., Barkley, R. M., Spraggins, J. M., Caprioli, R. M., & Murphy, R. C. (2011). MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chemical Reviews, 111, 6491–6512.Google Scholar
  17. 17.
    Börner, K., Malmberg, P., Månsson, J.-E., & Nygren, H. (2007). Molecular imaging of lipids in cells and tissues. International Journal of Mass Spectrometry, 260, 128–136.Google Scholar
  18. 18.
    Chaurand, P., Cornett, D. S., & Caprioli, R. M. (2006). Molecular imaging of thin mammalian tissue sections by mass spectrometry. Current Opinion in Biotechnology, 17, 431–436.PubMedGoogle Scholar
  19. 19.
    Wang, H.-Y. J., Liu, C. B., & Wu, H.-W. (2011). A simple desalting method for direct MALDI mass spectrometry profiling of tissue lipids. Journal of Lipid Research, 52, 840–849.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Colsch, B., Jackson, S. N., Dutta, S., & Woods, A. S. (2011). Molecular microscopy of brain gangliosides: Illustrating their distribution in hippocampal cell layers. ACS Chemical Neuroscience, 2, 213–222.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Woods, A. S., Colsch, B., Jackson, S. N., Post, J., Baldwin, K., Roux, A., et al. (2013). Gangliosides and ceramides change in a mouse model of blast induced traumatic brain injury. ACS Chemical Neuroscience, 4, 594–600.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Watrous, J. D., Alexandrov, T., & Dorrestein, P. C. (2011). The evolving field of imaging mass spectrometry and its impact on future biological research. Journal of Mass Spectrometry, 46, 209–222.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Ferguson, L., Bradshaw, R., Wolstenholme, R., Clench, M., & Francese, S. (2011). Two-step matrix application for the enhancement and imaging of latent fingermarks. Analytical Chemistry, 83, 5585–5591.PubMedGoogle Scholar
  24. 24.
    Schwamborn, K., & Caprioli, R. M. (2010). MALDI imaging mass spectrometry—Painting molecular pictures. Molecular Oncology, 4, 529–538.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Eberlin, L. S., Ferreira, C. R., Dill, A. L., Ifa, D. R., Cheng, L., & Cooks, R. G. (2011). Nondestructive, histologically compatible tissue imaging by desorption electrospray ionization mass spectrometry. Chembiochem, 12, 2129–2132.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Fuchs, B., Süs, R., & Schiller, J. (2010). An update of MALDI-TOF mass spectrometry in lipid research. Progress in Lipid Research, 49, 450–475.PubMedGoogle Scholar
  27. 27.
    Mccombie, G., & Knochenmuss, R. (2004). Small-molecule MALDI using the matrix suppression effect to reduce or eliminate matrix background interferences. Analytical Chemistry, 76, 4990–4997.PubMedGoogle Scholar
  28. 28.
    Eberlin, L. S., Liu, X., Ferreira, C. R., Santagata, S., Agar, N. Y. R., & Cooks, R. G. (2011). Desorption electrospray ionization then MALDI mass spectrometry imaging of lipid and protein distributions in single tissue sections. Analytical Chemistry, 83, 8366–8371.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Eberlin, L. S., Norton, I., Orringer, D., Dunn, I. F., Liu, X., Ide, J. L., et al. (2013). Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors. Proceedings of the National Academy of Sciences of the United States of America, 110, 1611–1616.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Marshall, A. G., Hendrickson, C. L., & Jackson, G. S. (1998). Fourier transform ion cyclotron resonance mass spectrometry: A primer. Mass Spectrometry Reviews, 17, 1–35.Google Scholar
  31. 31.
    Rujoi, M., Estrada, R., & Yappert, M. C. (2004). In situ MALDI-TOF MS regional analysis of neutral phospholipids in lens tissue. Analytical Chemistry, 76, 1657–1663.PubMedGoogle Scholar
  32. 32.
    Holthuis, J. C. M., Pomorski, T., Raggers, R. J., Sprong, H., & Van Meer, G. (2001). The organizing potential of sphingolipids in intracellular membrane transport. Physiological Reviews, 81, 1689–1723.PubMedGoogle Scholar
  33. 33.
    Buccoliero, R., & Futerman, A. H. (2003). The roles of ceramide and complex sphingolipids in neuronal cell function. Pharmacological Research, 47, 409–419.PubMedGoogle Scholar
  34. 34.
    Castellino, S. (2012). MALDI imaging MS analysis of drug distribution in tissue: The right time!(?). Bioanalysis, 4, 2549–2551.PubMedGoogle Scholar
  35. 35.
    Rasey, J. S., Krohn, K. A., Grunbaum, Z., Spence, A. M., Menard, T. W., & Wade, R. A. (1986). Synthesis, biodistribution, and autoradiography of radiolabeled S-2-(3-methylaminopropylamino)ethylphosphorothioic acid (Wr-3689). Radiation Research, 106, 366–379.PubMedGoogle Scholar
  36. 36.
    Solon, E. G., Schweitzer, A., Stoeckli, M., & Prideaux, B. (2009). Autoradiography, MALDI-MS, and SIMS-MS imaging in pharmaceutical discovery and development. The AAPS Journal, 12, 11–26.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Rudin, M., & Weissleder, R. (2003). Molecular imaging in drug discovery and development. Nature Reviews. Drug Discovery, 2, 123–131.PubMedGoogle Scholar
  38. 38.
    Castellino, S., Groseclose, M. R., & Wagner, D. (2011). MALDI imaging mass spectrometry: Bridging biology and chemistry in drug development. Bioanalysis, 3, 2427–2441.PubMedGoogle Scholar
  39. 39.
    Castellino, S., Groseclose, M. R., Sigafoos, J., Wagner, D., De Serres, M., Polli, J. W., et al. (2013). Central nervous system disposition and metabolism of fosdevirine (GSK2248761), a non-nucleoside reverse transcriptase inhibitor: An LC-MS and matrix-assisted laser desorption/ionization imaging MS investigation into central nervous system toxicity. Chemical Research in Toxicology, 26, 241–251.PubMedGoogle Scholar
  40. 40.
    Rubakhin, S. S., Jurchen, J. C., Monroe, E. B., & Sweedler, J. V. (2005). Imaging mass spectrometry: Fundamentals and applications to drug discovery. Drug Discovery Today, 10, 823–837.PubMedGoogle Scholar
  41. 41.
    Morosi, L., Spinelli, P., Zucchetti, M., Pretto, F., Carrà, A., D’Incalci, M., et al. (2013). Determination of paclitaxel distribution in solid tumors by nano-particle assisted laser desorption ionization mass spectrometry imaging. PLoS One, 8, E72532.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Gatti, R. A. (2012). SMRT compounds correct nonsense mutations in primary immunodeficiency and other genetic models. Annals of the New York Academy of Sciences, 1250, 33–40.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Chun, H. H., & Gatti, R. A. (2004). Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst), 3, 1187–1196.Google Scholar
  44. 44.
    Chun, H. H., Sun, X., Nahas, S. A., Teraoka, S., Lai, C.-H., Concannon, P., et al. (2003). Improved diagnostic testing for ataxia–telangiectasia by immunoblotting of nuclear lysates for ATM protein expression. Molecular Genetics and Metabolism, 80, 437–443.PubMedGoogle Scholar
  45. 45.
    Swift, M., Morrell, D., Cromartie, E., Chamberlin, A. R., Skolnick, M. H., & Bishop, D. T. (1986). The incidence and gene frequency of ataxia-telangiectasia in the United States. American Journal of Human Genetics, 39, 573–583.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Yoshizawa, S., Fourmy, D., & Puglisi, J. D. (1998). Structural origins of gentamicin antibiotic action. The EMBO Journal, 17, 6437–6448.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Barton-Davis, E. R., Shoturma, D. I., & Sweeney, H. L. (1999). Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle. Acta Physiologica Scandinavica, 167, 301–305.PubMedGoogle Scholar
  48. 48.
    Lai, C. H., Chun, H. H., Nahas, S. A., Mitui, M., Gamo, K. M., Du, L., et al. (2004). Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proceedings of the National Academy of Sciences of the United States of America, 101, 15676–15681.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Zingman, L. V., Park, S., Olson, T. M., Alekseev, A. E., & Terzic, A. (2007). Aminoglycoside-induced translational read-through in disease: Overcoming nonsense mutations by pharmacogenetic therapy. Clinical Pharmacology and Therapeutics, 81, 99–103.PubMedGoogle Scholar
  50. 50.
    Du, L., Damoiseaux, R., Nahas, S., Gao, K., Hu, H., Pollard, J. M., et al. (2009). Nonaminoglycoside compounds induce readthrough of nonsense mutations. The Journal of Experimental Medicine, 206, 2285–2297.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Du, L., Jung, M. E., Damoiseaux, R., Completo, G., Fike, F., Ku, J. M., et al. (2013). A new series of small molecular weight compounds induce read through of all three types of nonsense mutations in the ATM gene. Molecular Therapy, 21(9), 1653–1660.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Zoriy, M., Matusch, A., Spruss, T., & Becker, J. S. (2007). Laser ablation inductively coupled plasma mass spectrometry for imaging of copper, zinc, and platinum in thin sections of a kidney from a mouse treated with cis-platin. International Journal of Mass Spectrometry, 260, 102–106.Google Scholar
  53. 53.
    Zoriy, M. V., Dehnhardt, M., Matusch, A., & Becker, J. S. (2008). Comparative imaging of P, S, Fe, Cu, Zn and C in thin sections of rat brain tumor as well as control tissues by laser ablation inductively coupled plasma mass spectrometry. Spectrochimica Acta Part B: Atomic Spectroscopy, 63, 375–382.Google Scholar
  54. 54.
    Meng, H., Liong, M., Xia, T., Li, Z., Ji, Z., Zink, J. I., et al. (2010). Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano, 4, 4539–4550.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Yan, B., Kim, S. T., Kim, C. S., Saha, K., Moyano, D. F., Xing, Y., et al. (2013). Multiplexed imaging of nanoparticles in tissues using laser desorption/ionization mass spectrometry. Journal of the American Chemical Society, 135, 12564–12567.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Lear, J., Hare, D. J., Fryer, F., Adlard, P. A., Finkelstein, D. I., & Doble, P. A. (2012). High-resolution elemental bioimaging of Ca, Mn, Fe, Co, Cu, and Zn employing La-ICP-MS and hydrogen reaction gas. Analytical Chemistry, 84, 6707–6714.PubMedGoogle Scholar
  57. 57.
    Hutchinson, R. W., Cox, A. G., Mcleod, C. W., Marshall, P. S., Harper, A., Dawson, E. L., et al. (2005). Imaging and spatial distribution of Β-amyloid peptide and metal ions in Alzheimer’s plaques by laser ablation–inductively coupled plasma–mass spectrometry. Analytical Biochemistry, 346, 225–233.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Carly N. Ferguson
    • 1
  • Joseph W. M. Fowler
    • 1
  • Jonathan F. Waxer
    • 1
  • Richard A. Gatti
    • 2
    • 3
  • Joseph A. Loo
    • 1
    • 4
    Email author
  1. 1.Department of Chemistry and BiochemistryUniversity of California-Los AngelesLos AngelesUSA
  2. 2.Department of Pathology and Laboratory Medicine, David Geffen School of MedicineUniversity of California-Los AngelesLos AngelesUSA
  3. 3.Department of Human Genetics, David Geffen School of MedicineUniversity of California-Los AngelesLos AngelesUSA
  4. 4.Department of Biological Chemistry, David Geffen School of MedicineUniversity of California-Los AngelesLos AngelesUSA

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