Northeastern University

Drug/Metabolite quantification of cancer tissue samples using MALDI-MS

Daniela Ruiz with Dr. Nathalie Y.R. Agar (BWH)

Mass spectrometry Imaging (MSI) is a powerful analytical tool in science that is used to visualize molecular distributions of drugs, lipids, and metabolites in tissue samples. Specifically, Matrix assisted laser desorption/ionization (MALDI) is an emerging MSI modality due to its clinical-related applications such as metabolite quantitation, drug quantitation, and the analysis of the degree of drug penetration through the blood brain barrier. MALDI-MSI can do this by showing the distribution of small metabolites to large proteins with high spatial resolution. The research plan at the Agar Surgical Molecular imaging lab is to image drug and metabolite transit through the blood-brain barrier with the goal of developing new brain-penetrating agents. This approach uses different tissue samples from clinical trial patients treated with target therapy that undergoes H&E imaging and MALDI preparation/analysis as shown in Figure one. Additionally, a tissue mimetic is prepared using a tissue microarray mold with varying concentrations of drugs or related metabolites. The intensity response of each tissue sample along with the tissue mimetic will allow to mathematically create a calibration curve for the drug or metabolite quantification on each corresponding tissue section. The success of this project could potentially result in treatment of brain tumors to increase patient outcomes.