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.
Highlights
Tumor drug resistance has been ascribed for years to a number of mechanisms that influence the uptake, metabolism or proteins and drugs export from cells or change in the drug target[1,2]
The three-dimensional overview can give important clues about the mechanisms involved in a pathology
The last frontier of Mass spectrometry imaging (MSI) is the development of 3D model to deeper investigate the localization of endogenous compounds such as lipids[33,34] or proteins and peptides[26,35]
Summary
Tumor drug resistance has been ascribed for years to a number of mechanisms that influence the uptake, metabolism or proteins and drugs export from cells or change in the drug target[1,2]. Mass spectrometry imaging (MSI) is one of the latest, rapidly growing surface analysis techniques that permits the simultaneous visualization of multiple endogenous or exogenous compounds over a wide mass range, such as peptides and lipids and small molecules like metabolites or drugs, in cells and tissues[12,13].
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