Tissue biomarkers of drug efficacy: case studies using a MALDI-MSI workflow

Bioanalysis. 2015;7(20):2611-9. doi: 10.4155/bio.15.174. Epub 2015 Oct 27.

Abstract

MALDI MS imaging (MALDI-MSI) offers a capability to not only evaluate the distribution, localization and metabolism of drugs within tissues but also allow correlative tissue measurement of the effect of the drug on biomolecules in the targeted pathway. Particularly for MALDI-MSI, lipid molecules are readily detectable within tissues. Case study examples are provided for two different drugs targeting the sphingosine-1-phosphate/ceramide nexus in tumor xenograft tissues. A workflow combining high-resolution MALDI-MSI with on-tissue confirmation of targeted compounds using a structural library and on-tissue enzymatic digestion strategy is described. Representative images of drug metabolite distribution that correlate to an increase or decrease in sphingosine-1-phosphate or ceramide species are provided.

Publication types

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

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / analysis
  • Adamantane / metabolism
  • Adamantane / therapeutic use
  • Animals
  • Biomarkers, Tumor / analysis*
  • Ceramides / analysis
  • Ceramides / metabolism
  • Ceramides / therapeutic use
  • Disease Models, Animal
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Lysophospholipids / analysis
  • Mice
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Pyridines / analysis
  • Pyridines / metabolism
  • Pyridines / therapeutic use
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*
  • Sphingosine / analogs & derivatives
  • Sphingosine / analysis
  • Transplantation, Heterologous

Substances

  • 2-N-(6'-(1'-pyridinium)hexanoyl)sphingosine
  • Biomarkers, Tumor
  • Ceramides
  • Lysophospholipids
  • Pyridines
  • sphingosine 1-phosphate
  • 3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase 2, human
  • Sphingosine
  • Adamantane