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3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addr...

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Autores principales: Giordano, S., Morosi, L., Veglianese, P., Licandro, S. A., Frapolli, R., Zucchetti, M., Cappelletti, G., Falciola, L., Pifferi, V., Visentin, S., D’Incalci, M., Davoli, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107992/
https://www.ncbi.nlm.nih.gov/pubmed/27841316
http://dx.doi.org/10.1038/srep37027
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author Giordano, S.
Morosi, L.
Veglianese, P.
Licandro, S. A.
Frapolli, R.
Zucchetti, M.
Cappelletti, G.
Falciola, L.
Pifferi, V.
Visentin, S.
D’Incalci, M.
Davoli, E.
author_facet Giordano, S.
Morosi, L.
Veglianese, P.
Licandro, S. A.
Frapolli, R.
Zucchetti, M.
Cappelletti, G.
Falciola, L.
Pifferi, V.
Visentin, S.
D’Incalci, M.
Davoli, E.
author_sort Giordano, S.
collection PubMed
description Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.
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spelling pubmed-51079922016-11-22 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors Giordano, S. Morosi, L. Veglianese, P. Licandro, S. A. Frapolli, R. Zucchetti, M. Cappelletti, G. Falciola, L. Pifferi, V. Visentin, S. D’Incalci, M. Davoli, E. Sci Rep Article Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse. Nature Publishing Group 2016-11-14 /pmc/articles/PMC5107992/ /pubmed/27841316 http://dx.doi.org/10.1038/srep37027 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Giordano, S.
Morosi, L.
Veglianese, P.
Licandro, S. A.
Frapolli, R.
Zucchetti, M.
Cappelletti, G.
Falciola, L.
Pifferi, V.
Visentin, S.
D’Incalci, M.
Davoli, E.
3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
title 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
title_full 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
title_fullStr 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
title_full_unstemmed 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
title_short 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
title_sort 3d mass spectrometry imaging reveals a very heterogeneous drug distribution in tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107992/
https://www.ncbi.nlm.nih.gov/pubmed/27841316
http://dx.doi.org/10.1038/srep37027
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