Tissue biomarkers of drug efficacy: case studies using a MALDI-MSI workflow.
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.
Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Elizabeth Ellen
EE
Jones
Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Peng
P
Gao
Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Charles D
CD
Smith
Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
James S
JS
Norris
Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Richard R
RR
Drake
D000218:Adamantane / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002518:Ceramides / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008246:Lysophospholipids / Q000032:analysis; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013110:Sphingosine / Q000031:analogs & derivatives / Q000032:analysis; D014183:Transplantation, Heterologous; D000099157:Sphingosine Kinase
D000218:Adamantane; D014408:Biomarkers, Tumor; D002518:Ceramides; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D011725:Pyridines; D013110:Sphingosine; C578459:2-N-(6'-(1'-pyridinium)hexanoyl)sphingosine; C060506:sphingosine 1-phosphate; C548780:3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide; C000594250:sphingosine kinase 2, human; D000099157:Sphingosine Kinase