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

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.

• Authors: James J Connell, Yutaka Sugihara, Szilvia Török, Balázs Döme, József Tóvári, Thomas E Fehniger, György Marko-Varga, Ákos Végvári
• Journal: Analytical and bioanalytical chemistry (Anal Bioanal Chem) Vol. 407 Issue 8 Pg. 2245-53 (Mar 2015) ISSN: 1618-2650 [Electronic] Germany
• PMID: 25424181 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Indoles
• Pyrroles
• Sunitinib

Topics

• Angiogenesis Inhibitors (administration & dosage, pharmacokinetics)
• Animals
• Cell Line, Tumor
• Colonic Neoplasms (chemistry, drug therapy)
• Female
• Humans
• Indoles (administration & dosage, pharmacokinetics)
• Mice
• Mice, Inbred BALB C
• Molecular Imaging (methods)
• Pyrroles (administration & dosage, pharmacokinetics)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)
• Sunitinib