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Drug compound characterization by mass spectrometry imaging in cancer tissue

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Abstract

MALDI mass spectrometry imaging (MSI) provides a technology platform that allows the accurate visualization of unlabeled small molecules within the two-dimensional spaces of tissue samples. MSI has proven to be a powerful tool-box concept in the development of new drugs. MSI allows unlabeled drug compounds and drug metabolites to be detected and identified and quantified according to their mass-to-charge ratios (m/z) at high resolution in complex tissue environments. Such drug characterization in situ, by both spatial and temporal behaviors within tissue compartments, provide new understandings of the dynamic processes impacting drug uptake and metabolism at the local sites targeted by therapy. Further, MSI in combination with histology and immunohistochemistry, provides the added value of defining the context of cell biology present at the sites of drug localization thus providing invaluable information relating to treatment efficacy. In this report we provide mass spectrometry imaging data within various cancers such as malignant melanoma in patients administered with vemurafenib, a protein kinase inhibitor that is targeting BRAF mutated proteins and that has shown significant efficacy in restraining disease progression. We also provide an overview of other examples of the new generation of targeted drugs, and demonstrate the data on personalized medicine drugs localization within tumor compartments within in vivo models. In these cancer models we provide detailed data on drug and target protein co-localization of YCG185 and sunitinib. These drugs are targeting VEGFR2 within the angiogenesis mechanism. Our ability to resolve drug uptake at targeted sites of directed therapy provides important opportunities for increasing our understanding about the mode of action of drug activity within the environment of disease.

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Acknowledgments

This work was supported by grants from Mrs. Berta Kamprad Foundation, Swedish Academy of Pharmaceutical Sciences, Swedish Research Council, the Swedish Foundation for Strategic Research, Vinnova, Ingabritt & Arne Lundbergs forskningsstiftelse, Fundacion Federico SA, the Crafoord Foundation and from the National Research Foundation of Korea (NRF) funded by the Korean Government (2009-0083522 and 2012M3A9D1054520), and the Brain Korea 21 Plus Project, Republic of Korea.

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Authors and Affiliations

  1. Chemical Genomics National Research Lab, Department of Biotechnology, Translational Research Center for Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea

    Ho Jeong Kwon & Yonghyo Kim

  2. Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden

    Yutaka Sugihara, Bo Baldetorp & Charlotte Welinder

  3. Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan

    Ken-ichi Watanabe

  4. Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, Lund, Sweden

    Ken-ichi Watanabe, Toshihide Nishimura, Ákos Végvári, Thomas E. Fehniger & György Marko-Varga

  5. Centre of Excellence in Biological and Medical Mass Spectrometry “CEBMMS”, Biomedical Centre D13, Lund University, Lund, Sweden

    Toshihide Nishimura, Johan Malm, Thomas E. Fehniger & György Marko-Varga

  6. First Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo, Japan

    György Marko-Varga

  7. Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital in Malmö, Malmö, Sweden

    Johan Malm

  8. National Korányi Institute of Pulmonology, Budapest, Hungary

    Szilvia Török & Balázs Döme

  9. Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria

    Balázs Döme

  10. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA

    Ákos Végvári

  11. Department of Drug Metabolism, H. Lundbeck A/S, Copenhagen, Denmark

    Lena Gustavsson

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  1. Ho Jeong Kwon
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Correspondence to Johan Malm.

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Kwon, H.J., Kim, Y., Sugihara, Y. et al. Drug compound characterization by mass spectrometry imaging in cancer tissue. Arch. Pharm. Res. 38, 1718–1727 (2015). https://doi.org/10.1007/s12272-015-0627-2

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