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Drug Compound Characterization by Mass Spectrometry Imaging in Cancer Tissue

Kwon, Ho Jeong; Kim, Yanghyo; Sugihara, Yutaka LU ; Baldetorp, Bo LU ; Welinder, Charlotte LU ; Watanabe, Kenichi; Nishimura, Toshihide; Malm, Johan LU ; Török, Szilvia and Döme, Balázs, et al. (2015) In Archives of Pharmacal Research 38(9). p.1718-1727
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... (More)
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 both the BRAF, and ERK mutated target 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. (Less)
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Contribution to journal
publication status
published
subject
keywords
Mass spectrometry imaging, protein sequence, drug compound, cancer, malignant melanoma
in
Archives of Pharmacal Research
volume
38
issue
9
pages
1718 - 1727
publisher
Pharmaceutical Society of Korea
external identifiers
  • wos:000361445000014
  • scopus:84941996720
ISSN
1976-3786
DOI
10.1007/s12272-015-0627-2
language
English
LU publication?
yes
id
4bfb796b-2203-4c6d-b0bb-1f04609ddd9b (old id 7472289)
date added to LUP
2015-08-04 10:36:25
date last changed
2017-10-29 03:13:49
@article{4bfb796b-2203-4c6d-b0bb-1f04609ddd9b,
  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.<br/><br>
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.<br/><br>
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 both the BRAF, and ERK mutated target 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.<br/><br>
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 Kim, Yanghyo and Sugihara, Yutaka and Baldetorp, Bo and Welinder, Charlotte and Watanabe, Kenichi and Nishimura, Toshihide and Malm, Johan and Török, Szilvia and Döme, Balázs and Végvári, Ákos and Gustavsson, Lena and Fehniger, Thomas and Marko-Varga, György},
  issn         = {1976-3786},
  keyword      = {Mass spectrometry imaging,protein sequence,drug compound,cancer,malignant melanoma},
  language     = {eng},
  number       = {9},
  pages        = {1718--1727},
  publisher    = {Pharmaceutical Society of Korea},
  series       = {Archives of Pharmacal Research},
  title        = {Drug Compound Characterization by Mass Spectrometry Imaging in Cancer Tissue},
  url          = {http://dx.doi.org/10.1007/s12272-015-0627-2},
  volume       = {38},
  year         = {2015},
}