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Localization of sunitinib in in vivo animal and in vitro experimental models by MALDI mass spectrometry imaging

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Abstract

The spatial distribution of an anticancer drug and its intended target within a tumor plays a major role on determining how effective the drug can be at tackling the tumor. This study provides data regarding the lateral distribution of sunitinib, an oral antiangiogenic receptor tyrosine kinase inhibitor using an in vitro animal model as well as an in vitro experimental model that involved deposition of a solution of sunitinib onto tissue sections. All tumor sections were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging and compared with subsequent histology staining. Six tumors at four different time points after commencement of in vivo sunitinib treatment were examined to observe the patterns of drug uptake. The levels of sunitinib present in in vivo treated tumor sections increased continuously until day 7, but a decrease was observed at day 10. Furthermore, the in vitro experimental model was adjustable to produce a drug level similar to that obtained in the in vivo model experiments. The distribution of sunitinib in tissue sections treated in vitro appeared to agree with the histological structure of tumors, suggesting that this approach may be useful for testing drug update.

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Acknowledgments

AV is grateful for funding support Innovate Support 2011–03926 from CREATE Health. BD was supported by KTIA AIK 12-1-2013-0041, TÁMOP 424A/1-11-1-2012-0001, OTKA K109626, OTKA K108465, EUREKA_HU_12-1-2012-0057, ÖNB Jubiläumsfondsprojekt Nr. 14043, and the Vienna Fund for Innovative Interdisciplinary Cancer Research. JT was supported by OTKA K84173 and INNO 08-3-2009-0248 (2010).

Conflict of interest

The authors declare no potential conflicts of interest.

Author information

Author notes

  1. James J. Connell

    Present address: Biomedical Science, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland

Authors and Affiliations

  1. Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Biomedical Center D13, 221 84, Lund, Sweden

    James J. Connell, Thomas E. Fehniger, György Marko-Varga & Ákos Végvári

  2. Department of Oncology, Clinical Sciences, Lund University and Skåne University Hospital, 221 85, Lund, Sweden

    Yutaka Sugihara

  3. National Korányi Institute of Pulmonology, Budapest, 1121, Hungary

    Szilvia Török & Balázs Döme

  4. Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Szilvia Török & Balázs Döme

  5. Department of Thoracic Surgery, Semmelweis University-National Institute of Oncology, Ráth György u. 7-9, Budapest, 1122, Hungary

    Balázs Döme

  6. Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, 1090, Vienna, Austria

    Balázs Döme

  7. Department of Experimental Pharmacology, National Institute of Oncology, Ráth György u. 7-9, Budapest, 1122, Hungary

    József Tóvári

  8. Center of Excellence in Biological and Medical Mass Spectrometry, Lund University, BMC D13, Tornavägen 10, 221 84, Lund, Sweden

    Thomas E. Fehniger & György Marko-Varga

  9. First Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo, 160-0023, Japan

    György Marko-Varga

  10. CREATE Health, Lund University, 221 00, Lund, Sweden

    Ákos Végvári

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  1. James J. Connell
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  2. Yutaka Sugihara
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Correspondence to Ákos Végvári.

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Published in the topical collection Mass Spectrometry Imaging with guest editors Andreas Römpp and Uwe Karst.

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Connell, J.J., Sugihara, Y., Török, S. et al. Localization of sunitinib in in vivo animal and in vitro experimental models by MALDI mass spectrometry imaging. Anal Bioanal Chem 407, 2245–2253 (2015). https://doi.org/10.1007/s00216-014-8350-2

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  • DOI: https://doi.org/10.1007/s00216-014-8350-2

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