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Localization of sunitinib, its metabolites and its target receptors in tumor bearing mice: a MALDI mass spectrometry imaging study

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Author

  • Szilvia Török
  • Ákos Végvári
  • Melinda Rezeli
  • Thomas Fehniger
  • József Tóvári
  • Sándor Paku
  • Viktória László
  • Balázs Hegedüs
  • Anita Rózsás
  • Balázs Döme
  • György Marko-Varga
Show all

Summary, in English

A functional blood vessel network is essential for maintaining the necessary oxygen and nutrient levels in solid tumors. Thus, the inhibition of blood vessel growth by different antiangiogenic agents has become one of the most important topics in cancer research over the past few decades. The in vitro studies of these drugs are promising, but both the in vivo and the clinical experiences are controversial. Therefore, investigating the pharmacokinetic parameters of these compounds is a pivotal issue in drug development. In this study, the detection and the adsorption, distribution, metabolism, elimination (ADME) of the antiangiogenic receptor tyrosine kinase inhibitor (RTKI) sunitinib is analyzed in a subcutaneous syngeneic murine tumor model of colorectal cancer. The parent molecule of sunitinib was detected at m/z 399.218 with fragment ions at m/z 326.1 and 283.1 with matrix assisted laser desorption ionization (MALDI) technique. Metabolites of the drug were measured in blood samples and main metabolites were found in tumor, liver and kidney tissues at m/z 371.188, 397.203 and 415.214. Tissue distribution of the drug and its metabolites showed an overlapping pattern by MALDI imaging. The present study supports the role of the MALDI technique in the ADME characterization of drug candidates in preclinical drug development.

Publishing year

2015

Language

English

Pages

1148-1163

Publication/Series

British Journal of Pharmacology

Volume

172

Issue

4

Document type

Journal article

Publisher

Wiley

Topic

  • Pharmacology and Toxicology

Keywords

  • sunitinib
  • MALDI
  • imaging
  • mass spectrometry
  • angiogenesis
  • RTKI

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5381