Journal
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
Volume 29, Issue 3, Pages 516-526Publisher
AMER CHEMICAL SOC
DOI: 10.1007/s13361-017-1851-4
Keywords
MALDI-MSI; Colorectal tumor organoids; Irinotecan
Funding
- National Institutes of Health [R01GM110406]
- National Science Foundation (CAREER Award) [CHE-1351595]
- National Science Foundation [1625944]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1625944] Funding Source: National Science Foundation
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1827084] Funding Source: National Science Foundation
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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.
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