Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging

Sci Rep. 2013 Oct 4;3:2859. doi: 10.1038/srep02859.

Abstract

Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain - insights that would be difficult or impossible to extract by use of radiolabeled compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics
  • Biomarkers / metabolism
  • Blood-Brain Barrier / metabolism*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Disease Models, Animal
  • Erlotinib Hydrochloride
  • Glioma / metabolism
  • Glioma / pathology
  • Heme / metabolism
  • Heterografts
  • Humans
  • Mice
  • Molecular Imaging / methods*
  • Neovascularization, Pathologic
  • Optical Imaging / methods
  • Permeability
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacokinetics
  • Quinazolines / chemistry
  • Quinazolines / metabolism
  • Quinazolines / pharmacokinetics
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Pharmaceutical Preparations
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Protein Kinase Inhibitors
  • Quinazolines
  • Heme
  • Erlotinib Hydrochloride