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Quantitation of End...
Quantitation of Endogenous Metabolites in Mouse Tumors Using Mass-Spectrometry Imaging
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- Swales, John G. (författare)
- AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England;Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 1WB, S Yorkshire, England
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- Dexter, Alex (författare)
- Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England
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- Hamm, Gregory (författare)
- AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
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- Nilsson, Anna (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Strittmatter, Nicole (författare)
- AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
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- Michopoulos, Filippos (författare)
- AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
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- Hardy, Christopher (författare)
- AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
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- Morentin-Gutierrez, Pablo (författare)
- AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
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- Mellor, Martine (författare)
- AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
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- Andrén, Per E. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Clench, Malcolm R. (författare)
- Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 1WB, S Yorkshire, England
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- Bunch, Josephine (författare)
- Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England
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- Critchlow, Susan E. (författare)
- AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
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- Goodwin, Richard J. A. (författare)
- AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
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(creator_code:org_t)
- 2018-04-18
- 2018
- Engelska.
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 90:10, s. 6051-6058
- Relaterad länk:
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http://shura.shu.ac....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Described is a quantitative-mass-spectrometry-imaging (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 preanalysis-stabilization 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 degrees 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.
Ämnesord
- NATURVETENSKAP -- Kemi -- Analytisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Analytical Chemistry (hsv//eng)
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Swales, John G.
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Dexter, Alex
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Hamm, Gregory
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Nilsson, Anna
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Strittmatter, Ni ...
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Michopoulos, Fil ...
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visa fler...
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Hardy, Christoph ...
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Morentin-Gutierr ...
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Mellor, Martine
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Andrén, Per E.
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Clench, Malcolm ...
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Bunch, Josephine
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Critchlow, Susan ...
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Goodwin, Richard ...
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Analytical Chemi ...
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Uppsala universitet