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.

Clinical protein science in translational medicine targeting malignant melanoma

“…MALDI-MSI is more and more widely used to describing drug distributions in experimental systems. Nevertheless, more than 100 reports have been published where the technology has been used to characterise drug compounds in experimental drug predicting models (Connell et al 2015;Kwon et al 2015;Marko-Varga et al 2012a;Végvári et al 2017). Until recently, only our own studies have described such drug distribution in humans.…”

Clinical protein science developments for patient monitoring in hospital central laboratories

“…Especially MALDI links molecular analysis to traditional histology. MSI may add information to the histopathological analysis, confirm the diagnosis and aid in the choice of treatment [5]. Our knowledge of diseases is being advanced in large population-based studies, and the use of data from these epidemiological resources will highly impact our ability to both model and solve disease-related questions in the future.…”

Mass spectrometry imaging: An emerging technology for the analysis of metabolites in insects

“…Then, the ionization of each pixel on the surface of the sample was obtained by a mass analyzer (Ho, Shu, & Yang, ). Currently, MSI has been applied in many fields of life science, such as histology (Longuespée et al, ; Yalcin & de la Monte, ), pathology (Bowrey et al, ; Schubert, Weiland, Baune, & Hoffmann, ), pharmacology (Kwon et al, ; Liu & Hummon, ), plant science (Dong, Li, & Aharoni, ; Sturtevant, Lee, & Chapman, ), and microbiology (Shih, Chen, Liaw, Lai, & Yang, ; J. Y. Yang et al, ). Moreover, a number of papers have addressed the application of MSI in botany (Boughton, Thinagaran, Sarabia, Bacic, & Roessner, ; Qin et al, ), food science (Yoshimura, Goto‐Inoue, Moriyama, & Zaima, ), and biological interactions (Ho et al, ).…”

“…Then, the ionization of each pixel on the surface of the sample was obtained by a mass analyzer (Ho, Shu, & Yang, 2017). Currently, MSI has been applied in many fields of life science, such as histology (Longuespée et al, 2016;Yalcin & de la Monte, 2015), pathology (Bowrey et al, 2016;Schubert, Weiland, Baune, & Hoffmann, 2016), pharmacology (Kwon et al, 2015;Liu & Hummon, 2015), plant science (Dong, Li, & Aharoni, 2016;Sturtevant, Lee, & Chapman, 2016), and microbiology (Shih, Chen, Liaw, Lai, & Yang, 2014;J. Y. Yang et al, 2012).…”