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

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Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry. / Végvári, Ákos; Fehniger, Thomas E.; Rezeli, Melinda; Laurell, Thomas; Döme, Balazs; Jansson, Bo; Welinder, Charlotte; Marko-Varga, György.

I: Journal of Proteome Research, Vol. 12, Nr. 12, 2013, s. 5626-5633.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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TY - JOUR

T1 - Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry

AU - Végvári, Ákos

AU - Fehniger, Thomas E.

AU - Rezeli, Melinda

AU - Laurell, Thomas

AU - Döme, Balazs

AU - Jansson, Bo

AU - Welinder, Charlotte

AU - Marko-Varga, György

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Lung Cancer

KW - Adenocarcinoma

KW - MALDI-Mass Spectrometry Imaging

KW - Erlotinib

KW - Gefitinib

KW - Tiotropium

U2 - 10.1021/pr400581b

DO - 10.1021/pr400581b

M3 - Article

VL - 12

SP - 5626

EP - 5633

JO - Journal of Proteome Research

T2 - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 12

ER -