Skip to main content

Applications of Mass Spectrometry Imaging for Safety Evaluation

  • Protocol
  • First Online:
Drug Safety Evaluation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1641))

Abstract

Mass spectrometry imaging (MSI) was first derived from techniques used in physics, which were then incorporated into chemistry followed by application in biology. Developed over 50 years ago, and with different principles to detect and map compounds on a sample surface, MSI supports modern biology questions by detecting biological compounds within tissue sections. MALDI (matrix-assisted laser desorption/ionization) imaging trend analysis in this field shows an important increase in the number of publications since 2005, especially with the development of the MALDI imaging technique and its applications in biomarker discovery and drug distribution. With recent improvements of statistical tools, absolute and relative quantification protocols, as well as quality and reproducibility evaluations, MALDI imaging has become one of the most reliable MSI techniques to support drug discovery and development phases. MSI allows to potentially address important questions in drug development such as “What is the localization of the drug and its metabolites in the tissues?”, “What is the pharmacological effect of the drug in this particular region of interest?”, or “Is the drug and its metabolites related to an atypical finding?” However, prior to addressing these questions using MSI techniques, expertise needs to be developed to become proficient at histological procedures (tissue preparation with frozen of fixed tissues), analytical chemistry, matrix application, instrumentation, informatics, and mathematics for data analysis and interpretation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Caprioli R, Farmer T, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69(23):4751–4760

    Article  CAS  PubMed  Google Scholar 

  2. Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7(4):493–496

    Article  CAS  PubMed  Google Scholar 

  3. Chaurand P, Schwartz SA, Caprioli RM (2002) Imaging mass spectrometry: a new tool to investigate the spatial organization of peptides and proteins in mammalian tissue sections. Curr Opin Chem Biol 6(5):676–681

    Article  CAS  PubMed  Google Scholar 

  4. Chaurand P, Cornett DS, Caprioli RM (2006) Molecular imaging of thin mammalian tissue sections by mass spectrometry. Curr Opin Biotechnol 17(4):431–436

    Article  CAS  PubMed  Google Scholar 

  5. Lemaire R, Menguellet SA, Stauber J, Marchaudon V, Lucot JP, Collinet P, Farine MO, Vinatier D, Day R, Ducoroy P, Salzet M, Fournier I (2007) Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker. J Proteome Res 6(11):4127–4134

    Article  CAS  PubMed  Google Scholar 

  6. Stoeckli M, Staab D, Schweitzer A (2007) Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections. Int J Mass Spectrom 260(2–3):195–202

    Article  CAS  Google Scholar 

  7. Cornett D, Frappier S, Caprioli R (2008) MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal Chem 80(14):5648–5653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Groseclose MR, Massion PP, Chaurand P, Caprioli RM (2008) High-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue microarrays using MALDI imaging mass spectrometry. Proteomics 8(18):3715–3724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Franck J, Arafah K, Elayed M, Bonnel D, Vergara D, Jacquet A, Vinatier D, Wisztorski M, Day R, Fournier I, Salzet M (2009) MALDI imaging mass spectrometry: state of the art technology in clinical proteomics. Mol Cell Proteomics 8(9):2023–2033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Grey AC, Chaurand P, Caprioli RM, Schey KL (2009) MALDI imaging mass spectrometry of integral membrane proteins from ocular lens and retinal tissue. J Proteome Res 8(7):3278–3283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Solon EG, Schweitzer A, Stoeckli M, Prideaux B (2010) Autoradiography, MALDI-MS, and SIMS-MS imaging in pharmaceutical discovery and development. AAPS J 12(1):11–26

    Article  CAS  PubMed  Google Scholar 

  12. Bonnel D, Legouffe R, Willand N, Baulard A, Hamm G, Deprez B, Stauber J (2011) MALDI imaging techniques dedicated to drug-distribution studies. Bioanalysis 3(12):1399–1406

    Article  CAS  PubMed  Google Scholar 

  13. Bonnel D, Longuespee R, Franck J, Roudbaraki M, Gosset P, Day R, Salzet M, Fournier I (2011) Multivariate analyses for biomarkers hunting and validation through on-tissue bottom-up or in-source decay in MALDI-MSI: application to prostate cancer. Anal Bioanal Chem 401(1):149–165

    Article  CAS  PubMed  Google Scholar 

  14. Seeley EH, Caprioli RM (2011) MALDI imaging mass spectrometry of human tissue: method challenges and clinical perspectives. Trends Biotechnol 29(3):136–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brignole-Baudouin F, Desbenoit N, Hamm G, Liang H, Both J-P, Brunelle A, Fournier I, Guerineau V, Legouffe R, Stauber J, Touboul D, Wisztorski M, Salzet M, Laprevote O, Baudouin C (2012) A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an Experimental Study in Rabbits. PLoS One 7(11):e50180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kreye F, Hamm G, Karrout Y, Legouffe R, Bonnel D, Siepmann F, Siepmann J (2012) MALDI-TOF MS imaging of controlled release implants. J Control Release 161(1):98–108

    Article  CAS  PubMed  Google Scholar 

  17. Prideaux B, Stoeckli M (2012) Mass spectrometry imaging for drug distribution studies. J Proteome 75(16):4999–5013

    Article  CAS  Google Scholar 

  18. Navis AC, Niclou SP, Fack F, Stieber D, van Lith S, Verrijp K, Wright A, Stauber J, Tops B, Otte-Holler I, Wevers RA, van Rooij A, Pusch S, von Deimling A, Tigchelaar W, van Noorden CJ, Wesseling P, Leenders WP (2013) Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model: in situ detection of 2-HG and alpha-KG. Acta Neuropathol Commun 1:18

    Article  PubMed  PubMed Central  Google Scholar 

  19. Anderson DG, Ablonczy Z, Koutalos Y, Spraggins J, Crouch R, Caprioli R, Schey K (2014) High resolution MALDI imaging mass spectrometry of retinal tissue lipids. J Am Soc Mass Spectrom 25(8):1394–1403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miyamoto S, Hsu C-C, Hamm G, Darshi M, Diamond-Stanic M, Declèves A-E, Slater L, Pennathur S, Stauber J, Dorrestein PC, Sharma K (2016) Mass spectrometry imaging reveals elevated glomerular ATP/AMP in diabetes/obesity and identifies sphingomyelin as a possible mediator. EBioMedicine 7:121–134

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sun N, Fernandez IE, Wei M, Wu Y, Aichler M, Eickelberg O, Walch A (2016) Pharmacokinetic and pharmacometabolomic study of pirfenidone in normal mouse tissues using high mass resolution MALDI-FTICR-mass spectrometry imaging. Histochem Cell Biol 145(2):201–211

    Article  CAS  PubMed  Google Scholar 

  22. Groseclose MR, Laffan SB, Frazier KS, Hughes-Earle A, Castellino S (2015) Imaging MS in toxicology: an investigation of juvenile rat nephrotoxicity associated with dabrafenib administration. J Am Soc Mass Spectrom 26:887–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hamm G, Bonnel D, Legouffe R, Pamelard F, Delbos J-M, Bouzom F, Stauber J (2012) Quantitative mass spectrometry imaging of propranolol and olanzapine using tissue extinction calculation as normalization factor. J Proteome 75(16):4952–4961

    Article  CAS  Google Scholar 

  24. Pirman DA, Reich RF, Kiss A, Heeren RMA, Yost RA (2012) Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard. Anal Chem 85(2):1081–1089

    Article  PubMed  Google Scholar 

  25. Groseclose MR, Castellino S (2013) A mimetic tissue model for the quantification of drug distributions by MALDI imaging mass spectrometry. Anal Chem 85(21):10099–10106

    Article  CAS  PubMed  Google Scholar 

  26. Chumbley CW, Reyzer ML, Allen JL, Marriner GA, Via LE, Barry CE 3rd, Caprioli RM (2016) Absolute quantitative MALDI imaging mass spectrometry: a case of rifampicin in liver tissues. Anal Chem 88(4):2392–2398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stauber J (2013) Quantitation by MS imaging: needs and challenges in pharmaceuticals. Bioanalysis 4(17):2095–2098

    Article  Google Scholar 

  28. Lemaire R, Desmons A, Tabet JC, Day R, Salzet M, Fournier I (2007) Direct analysis and MALDI imaging of formalin-fixed, paraffin-embedded tissue sections. J Proteome Res 6(4):1295–1305

    Article  CAS  PubMed  Google Scholar 

  29. Stauber J, Lemaire R, Franck J, Bonnel D, Croix D, Day R, Wisztorski M, Fournier I, Salzet M (2008) MALDI imaging of formalin-fixed paraffin-embedded tissues: application to model animals of Parkinson disease for biomarker hunting. J Proteome Res 7(3):969–978

    Article  CAS  PubMed  Google Scholar 

  30. Goodwin RJA, Iverson SL, Andren PE (2012) The significance of ambient-temperature on pharmaceutical and endogenous compound abundance and distribution in tissues sections when analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging. Rapid Commun Mass Spec 26(5):494–498

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Juliette Masure for the technical support and Stefan Linehan for his comments that greatly improved the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jonathan Stauber .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Bonnel, D., Stauber, J. (2017). Applications of Mass Spectrometry Imaging for Safety Evaluation. In: Gautier, JC. (eds) Drug Safety Evaluation. Methods in Molecular Biology, vol 1641. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7172-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7172-5_6

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7170-1

  • Online ISBN: 978-1-4939-7172-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics