title: Drug compound characterization by mass spectrometry imaging in cancer tissue.
abstract: MALDI mass spectrometry imaging (MSI) provides a technology platform that allows the accurate visualization of unlabeled small molecules within the two-dimensional spaces of tissue samples. MSI has proven to be a powerful tool-box concept in the development of new drugs. MSI allows unlabeled drug compounds and drug metabolites to be detected and identified and quantified according to their mass-to-charge ratios (m/z) at high resolution in complex tissue environments. Such drug characterization in situ, by both spatial and temporal behaviors within tissue compartments, provide new understandings of the dynamic processes impacting drug uptake and metabolism at the local sites targeted by therapy. Further, MSI in combination with histology and immunohistochemistry, provides the added value of defining the context of cell biology present at the sites of drug localization thus providing invaluable information relating to treatment efficacy. In this report we provide mass spectrometry imaging data within various cancers such as malignant melanoma in patients administered with vemurafenib, a protein kinase inhibitor that is targeting BRAF mutated proteins and that has shown significant efficacy in restraining disease progression. We also provide an overview of other examples of the new generation of targeted drugs, and demonstrate the data on personalized medicine drugs localization within tumor compartments within in vivo models. In these cancer models we provide detailed data on drug and target protein co-localization of YCG185 and sunitinib. These drugs are targeting VEGFR2 within the angiogenesis mechanism. Our ability to resolve drug uptake at targeted sites of directed therapy provides important opportunities for increasing our understanding about the mode of action of drug activity within the environment of disease.
authors.affiliation: Chemical Genomics National Research Lab, Department of Biotechnology, Translational Research Center for Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Chemical Genomics National Research Lab, Department of Biotechnology, Translational Research Center for Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Yonghyo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sugihara
authors.affiliation: Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Baldetorp
authors.affiliation: Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Welinder
authors.affiliation: Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.|Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, Lund, Sweden.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, Lund, Sweden.|Centre of Excellence in Biological and Medical Mass Spectrometry "CEBMMS", Biomedical Centre D13, Lund University, Lund, Sweden.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Centre of Excellence in Biological and Medical Mass Spectrometry "CEBMMS", Biomedical Centre D13, Lund University, Lund, Sweden. johan.malm@med.lu.se.|Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital in Malmö, Malmö, Sweden. johan.malm@med.lu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Malm
authors.affiliation: National Korányi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Török
authors.affiliation: National Korányi Institute of Pulmonology, Budapest, Hungary.|Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Balázs
authors.initials: B
authors.lastname: Döme
authors.affiliation: Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, Lund, Sweden.|Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Végvári
authors.affiliation: Department of Drug Metabolism, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Gustavsson
authors.affiliation: Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, Lund, Sweden.|Centre of Excellence in Biological and Medical Mass Spectrometry "CEBMMS", Biomedical Centre D13, Lund University, Lund, Sweden.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Fehniger
authors.affiliation: Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, Lund, Sweden.|Centre of Excellence in Biological and Medical Mass Spectrometry "CEBMMS", Biomedical Centre D13, Lund University, Lund, Sweden.|First Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo, Japan.
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D004339:Drug Compounding / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D057285:Precision Medicine / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D000077210:Sunitinib; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib
keywords: Cancer; Drug compound; Malignant melanoma; Mass spectrometry imaging; Protein sequence