Drug localization in different lung cancer phenotypes by MALDI mass spectrometry imaging

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

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79 Citations (Scopus)

Abstract

Lung cancer is a common cause of cancer mortality in the world, largely due to the risk factor of tobacco smoking. The drug therapy at the molecular level includes targeting the epidermal growth factor receptor (EGFR) tyrosine kinase activity by using inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa). The heterogeneity of disease phenotypes and the somatic mutations presented in patient populations have a great impact on the efficacy of treatments using targeted personalized medicine.In this study, we report on basic physical and chemical properties of erlotinib and gefitinib in three different lung cancer tumor phenotypes, using MALDI instrumentation in imaging mode, providing spatial localization of drugs without chemical labeling. Erlotinib and gefitinib were analyzed in i) planocellular lung carcinoma, ii) adenocarcinoma and iii) large cell lung carcinoma following their deposition on the tissue surfaces by piezo-dispensing, using a controlled procedure. The importance of high-resolution sampling was crucial in order to accurately localize the EGFR tyrosine kinase inhibitors deposited in heterogeneous cancer tissue compartments.This is the first report on personalized drug characterization with localizations at a lateral resolution of 30. μm, which allowed us to map these compounds at attomolar concentrations within the lung tumor tissue microenvironments.

Original languageEnglish
Pages (from-to)982-992
Number of pages11
JournalJournal of proteomics
Volume74
Issue number7
DOIs
Publication statusPublished - Jun 10 2011

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Keywords

  • Erlotinib
  • Gefitinib
  • Lung cancer
  • MALDI-MS imaging

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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