Drug compound characterization by mass spectrometry imaging in cancer tissue

Ho Jeong Kwon, Yonghyo Kim, Yutaka Sugihara, Bo Baldetorp, Charlotte Welinder, Ken Ichi Watanabe, Toshihide Nishimura, Johan Malm, Szilvia Török, Balázs Döme, Ákos Végvári, Lena Gustavsson, Thomas E. Fehniger, György Marko-Varga

Research output: Contribution to journalReview article

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1718-1727
Number of pages10
JournalArchives of pharmacal research
Volume38
Issue number9
DOIs
Publication statusPublished - 2015 Sep 22

Fingerprint

Mass spectrometry
Mass Spectrometry
Tissue
Imaging techniques
Pharmaceutical Preparations
Neoplasms
Spatial Behavior
Cytology
Precision Medicine
Histology
Aptitude
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Drug Delivery Systems
Protein Kinase Inhibitors
Metabolites
Metabolism
Medicine
Cell Biology
Disease Progression
Tumors

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Cite this

Kwon, H. J., Kim, Y., Sugihara, Y., Baldetorp, B., Welinder, C., Watanabe, K. I., ... Marko-Varga, G. (2015). Drug compound characterization by mass spectrometry imaging in cancer tissue. Archives of pharmacal research, 38(9), 1718-1727. https://doi.org/10.1007/s12272-015-0627-2
Kwon, Ho Jeong ; Kim, Yonghyo ; Sugihara, Yutaka ; Baldetorp, Bo ; Welinder, Charlotte ; Watanabe, Ken Ichi ; Nishimura, Toshihide ; Malm, Johan ; Török, Szilvia ; Döme, Balázs ; Végvári, Ákos ; Gustavsson, Lena ; Fehniger, Thomas E. ; Marko-Varga, György. / Drug compound characterization by mass spectrometry imaging in cancer tissue. In: Archives of pharmacal research. 2015 ; Vol. 38, No. 9. pp. 1718-1727.
@article{9d91236e28fa4e9d9738c13c356d628f,
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.",
author = "Kwon, {Ho Jeong} and Yonghyo Kim and Yutaka Sugihara and Bo Baldetorp and Charlotte Welinder and Watanabe, {Ken Ichi} and Toshihide Nishimura and Johan Malm and Szilvia T{\"o}r{\"o}k and Bal{\'a}zs D{\"o}me and {\'A}kos V{\'e}gv{\'a}ri and Lena Gustavsson and Fehniger, {Thomas E.} and Gy{\"o}rgy Marko-Varga",
year = "2015",
month = "9",
day = "22",
doi = "10.1007/s12272-015-0627-2",
language = "English",
volume = "38",
pages = "1718--1727",
journal = "Archives of Pharmacal Research",
issn = "0253-6269",
publisher = "Pharmaceutical Society of Korea",
number = "9",

}

Kwon, HJ, Kim, Y, Sugihara, Y, Baldetorp, B, Welinder, C, Watanabe, KI, Nishimura, T, Malm, J, Török, S, Döme, B, Végvári, Á, Gustavsson, L, Fehniger, TE & Marko-Varga, G 2015, 'Drug compound characterization by mass spectrometry imaging in cancer tissue', Archives of pharmacal research, vol. 38, no. 9, pp. 1718-1727. https://doi.org/10.1007/s12272-015-0627-2

Drug compound characterization by mass spectrometry imaging in cancer tissue. / Kwon, Ho Jeong; Kim, Yonghyo; Sugihara, Yutaka; Baldetorp, Bo; Welinder, Charlotte; Watanabe, Ken Ichi; Nishimura, Toshihide; Malm, Johan; Török, Szilvia; Döme, Balázs; Végvári, Ákos; Gustavsson, Lena; Fehniger, Thomas E.; Marko-Varga, György.

In: Archives of pharmacal research, Vol. 38, No. 9, 22.09.2015, p. 1718-1727.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Drug compound characterization by mass spectrometry imaging in cancer tissue

AU - Kwon, Ho Jeong

AU - Kim, Yonghyo

AU - Sugihara, Yutaka

AU - Baldetorp, Bo

AU - Welinder, Charlotte

AU - Watanabe, Ken Ichi

AU - Nishimura, Toshihide

AU - Malm, Johan

AU - Török, Szilvia

AU - Döme, Balázs

AU - Végvári, Ákos

AU - Gustavsson, Lena

AU - Fehniger, Thomas E.

AU - Marko-Varga, György

PY - 2015/9/22

Y1 - 2015/9/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84941996720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941996720&partnerID=8YFLogxK

U2 - 10.1007/s12272-015-0627-2

DO - 10.1007/s12272-015-0627-2

M3 - Review article

VL - 38

SP - 1718

EP - 1727

JO - Archives of Pharmacal Research

JF - Archives of Pharmacal Research

SN - 0253-6269

IS - 9

ER -