Experimental models to study drug distributions in tissue using MALDI mass spectrometry imaging

Ákos Végvári, Thomas E. Fehniger, Melinda Rezeli, Thomas Laurell, Balázs Döme, Bo Jansson, Charlotte Welinder, György Marko-Varga

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within microenvironmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva) and gefitinib (Iressa), and the acetylcholine receptor antagonist, tiotropium, were characterized by microenvironment localization. Intact tissue blocks were also immersed in drug solution, followed by sectioning. MALDI-MSI was then performed using a Thermo MALDI LTQ Orbitrap XL instrument to localize drug-distribution patterns. We propose three MALDI-MSI models measuring drug disposition that have been used to map the selected compounds within tissue compartments of tumors isolated from lung cancer patients.

Original languageEnglish
Pages (from-to)5626-5633
Number of pages8
JournalJournal of Proteome Research
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 6 2013

Keywords

  • MALDI-mass spectrometry imaging
  • adenocarcinoma
  • erlotinib
  • gefitinib
  • lung cancer
  • tiotropium

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint Dive into the research topics of 'Experimental models to study drug distributions in tissue using MALDI mass spectrometry imaging'. Together they form a unique fingerprint.

  • Cite this

    Végvári, Á., Fehniger, T. E., Rezeli, M., Laurell, T., Döme, B., Jansson, B., Welinder, C., & Marko-Varga, G. (2013). Experimental models to study drug distributions in tissue using MALDI mass spectrometry imaging. Journal of Proteome Research, 12(12), 5626-5633. https://doi.org/10.1021/pr400581b