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

S. Giordano, L. Morosi, P. Veglianese, S. A. Licandro, R. Frapolli, M. Zucchetti, G. Cappelletti, L. Falciola, V. Pifferi, S. Visentin, M. D'Incalci, E. Davoli

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number37027
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Nov 14 2016

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Mass Spectrometry
Pharmaceutical Preparations
Neoplasms
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Paclitaxel
Tumor Burden
High Pressure Liquid Chromatography
Recurrence

ASJC Scopus subject areas

  • General

Cite this

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.

In: Scientific Reports, Vol. 6, 37027, 14.11.2016.

Research output: Contribution to journalArticle

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. In: Scientific Reports. 2016 ; Vol. 6.
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