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Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry

Végvári, Ákos LU ; Fehniger, Thomas E.; Rezeli, Melinda LU ; Laurell, Thomas LU ; Döme, Balazs; Jansson, Bo; Welinder, Charlotte LU and Marko-Varga, György LU (2013) In Journal of Proteome Research 12(12). p.5626-5633
Abstract
Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within micro-environmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva™) and gefitinib (Iressa™), and the acetylcholine receptor antagonist, tiotropium were... (More)
Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within micro-environmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva™) and gefitinib (Iressa™), and the acetylcholine receptor antagonist, tiotropium were characterized by microenvironment localization. Intact tissue blocks were also immersed in drug solution followed by sectioning. MALDI-MSI was then performed using a Thermo MALDI LTQ Orbitrap XL instrument to localize drug distribution patterns. We propose three MALDI-MSI models measuring drug disposition that have been used to map the selected compounds within tissue compartments of tumors isolated from lung cancer patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lung Cancer, Adenocarcinoma, MALDI-Mass Spectrometry Imaging, Erlotinib, Gefitinib, Tiotropium
in
Journal of Proteome Research
volume
12
issue
12
pages
5626 - 5633
publisher
The American Chemical Society
external identifiers
  • wos:000328231300024
  • scopus:84890104949
ISSN
1535-3893
DOI
10.1021/pr400581b
language
English
LU publication?
yes
id
14b7a42c-fb6e-45df-96e2-49f8feb89ab9 (old id 4193466)
date added to LUP
2014-01-07 10:52:45
date last changed
2019-03-13 10:51:46
@article{14b7a42c-fb6e-45df-96e2-49f8feb89ab9,
  abstract     = {Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within micro-environmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva™) and gefitinib (Iressa™), and the acetylcholine receptor antagonist, tiotropium were characterized by microenvironment localization. Intact tissue blocks were also immersed in drug solution followed by sectioning. MALDI-MSI was then performed using a Thermo MALDI LTQ Orbitrap XL instrument to localize drug distribution patterns. We propose three MALDI-MSI models measuring drug disposition that have been used to map the selected compounds within tissue compartments of tumors isolated from lung cancer patients.},
  author       = {Végvári, Ákos and Fehniger, Thomas E. and Rezeli, Melinda and Laurell, Thomas and Döme, Balazs and Jansson, Bo and Welinder, Charlotte and Marko-Varga, György},
  issn         = {1535-3893},
  keyword      = {Lung Cancer,Adenocarcinoma,MALDI-Mass Spectrometry Imaging,Erlotinib,Gefitinib,Tiotropium},
  language     = {eng},
  number       = {12},
  pages        = {5626--5633},
  publisher    = {The American Chemical Society},
  series       = {Journal of Proteome Research},
  title        = {Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry},
  url          = {http://dx.doi.org/10.1021/pr400581b},
  volume       = {12},
  year         = {2013},
}