MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal Tumor Organoids

Article

Abstract

Patient-derived colorectal tumor organoids (CTOs) closely recapitulate the complex morphological, phenotypic, and genetic features observed in in vivo tumors. Therefore, evaluation of drug distribution and metabolism in this model system can provide valuable information to predict the clinical outcome of a therapeutic response in individual patients. In this report, we applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to examine the spatial distribution of the drug irinotecan and its metabolites in CTOs from two patients. Irinotecan is a prodrug and is often prescribed as part of therapeutic regimes for patients with advanced colorectal cancer. Irinotecan shows a time-dependent and concentration-dependent permeability and metabolism in the CTOs. More interestingly, the active metabolite SN-38 does not co-localize well with the parent drug irinotecan and the inactive metabolite SN-38G. The phenotypic effect of irinotecan metabolism was also confirmed by a viability study showing significantly reduced proliferation in the drug treated CTOs. MALDI-MSI can be used to investigate various pharmaceutical compounds in CTOs derived from different patients. By analyzing multiple CTOs from a patient, this method could be used to predict patient-specific drug responses and help to improve personalized dosing regimens.

Attributes

Attribute NameValues
Creator
  • Colin Flinders

  • Shannon M. Mumenthaler

  • Amanda B. Hummon

  • Xin Liu

Journal or Work Title
  • Journal of the American Society for Mass Spectrometry

Volume
  • 29

Issue
  • 3

First Page
  • 516

Last Page
  • 526

Number of Pages
  • 10

ISSN
  • 1044-0305

eISSN
  • 1879-1123

Publication Date
  • 2018-03

Publisher
  • Springer US

Date Created
  • 2018-10-31

Language
  • English

Departments and Units
Record Visibility and Access Public
Content License
  • All rights reserved

Digital Object Identifier

doi:10.1007/s13361-017-1851-4

This DOI is the best way to cite this article.