Quantitation of endogenous metabolites in mouse tumors using mass-spectrometry imaging

SWALES, John, DEXTER, Alex, HAMM, Gregory, NILSSON, Anna, STRITTMATTER, Nicole, MICHOPOULOS, Filippos, HARDY, Christopher, MORENTIN-GUTIERREZ, Pablo, MELLOR, Martine, ANDREN, Per E., CLENCH, Malcolm, BUNCH, Josephine, CRITCHLOW, Susan E. and GOODWIN, Richard J. A. (2018). Quantitation of endogenous metabolites in mouse tumors using mass-spectrometry imaging. Analytical Chemistry, 90 (10), 6051-6058.

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Official URL: https://pubs.acs.org/doi/10.1021/acs.analchem.7b05...
Link to published version:: https://doi.org/10.1021/acs.analchem.7b05239

Abstract

Described is a quantitative-mass-spectrometryimaging (qMSI) methodology for the analysis of lactate and glutamate distributions in order to delineate heterogeneity among mouse tumor models used to support drug-discovery efficacy testing. We evaluate and report on preanalysisstabilization methods aimed at improving the reproducibility and efficiency of quantitative assessments of endogenous molecules in tissues. Stability experiments demonstrate that optimum stabilization protocols consist of frozen-tissue embedding, post-tissue-sectioning desiccation, and storage at −80 °C of tissue sections sealed in vacuum-tight containers. Optimized stabilization protocols are used in combination with qMSI methodology for the absolute quantitation of lactate and glutamate in tumors, incorporating the use of two different stable-isotope-labeled versions of each analyte and spectral-clustering performed on each tissue section using k-means clustering to allow region-specific, pixel-by-pixel quantitation. Region-specific qMSI was used to screen different tumor models and identify a phenotype that has low lactate heterogeneity, which will enable accurate measurements of lactate modulation in future drug-discovery studies. We conclude that using optimized qMSI protocols, it is possible to quantify endogenous metabolites within tumors, and region-specific quantitation can provide valuable insight into tissue heterogeneity and the tumor microenvironment.

Item Type: Article
Additional Information: ** From Crossref via Jisc Publications Router.
Uncontrolled Keywords: Analytical Chemistry
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: https://doi.org/10.1021/acs.analchem.7b05239
SWORD Depositor: Margaret Boot
Depositing User: Margaret Boot
Date Deposited: 11 May 2018 13:41
Last Modified: 21 Jul 2018 19:30
URI: http://shura.shu.ac.uk/id/eprint/21030

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