title: Experimental models to study drug distributions in tissue using MALDI mass spectrometry imaging.
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 microenvironmental 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.
authors.affiliation: Clinical Protein Science & Imaging, Biomedical Center, Department of Measurement Technology and Industrial Electrical Engineering, Lund University , BMC C13, SE-221 84 Lund, Sweden.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Végvári
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Fehniger
authors.forename: Melinda
authors.initials: M
authors.lastname: Rezeli
authors.forename: Thomas
authors.initials: T
authors.lastname: Laurell
authors.forename: Balázs
authors.initials: B
authors.lastname: Döme
authors.forename: Bo
authors.initials: B
authors.lastname: Jansson
authors.forename: Charlotte
authors.initials: C
authors.lastname: Welinder
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D018680:Cholinergic Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008867:Microtomy; D009374:Neoplasms, Experimental; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D012602:Scopolamine Derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000069447:Tiotropium Bromide; D046509:Tissue Culture Techniques; D059016:Tumor Microenvironment
chemical_list: D018680:Cholinergic Antagonists; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012602:Scopolamine Derivatives; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D000069447:Tiotropium Bromide