Imaging mass spectrometry in drug development and toxicology

Abstract

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

Combining MALDI‐2 and transmission geometry laser optics to achieve high sensitivity for ultra‐high spatial resolution surface analysis

“…Matrix-assisted laser/desorption ionization (MALDI) mass spectrometry (MS) is a technology that enables the spatial analysis of tissues with a high degree of molecular specificity, enabling new approaches for understanding biology and medicine. [1][2][3] Tissue interrogation by MALDI is performed by either collecting individual spectra from discrete foci as a histology guided profiling experiment 4,5 or by rastering the sample to collect spectra over an area of the sample to generate ion images. 6,7 In either case, cell-scale interrogation of the sample (<10 μm) is desired to differentiate among cell types for complete characterization of a tissue.…”

Accessible and reproducible mass spectrometry imaging data analysis in Galaxy

“…Depending on the sample, the analyte of interest and the application, different mass spectrometers are used [6]. The most common ionization sources are MALDI (Matrix Due to the variety of samples, analytes, and mass spectrometers, MSI is suitable for highly diverse use cases ranging from plant research, to (pre-)clinical, pharmacologic studies, and forensic investigations [2,[7][8][9]. On the other hand, the variety of research fields hinders harmonization and standardization of MSI protocols.…”

Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes

“…More experiments employing “inert” compounds (such as oxantel pamoate, which do almost not leave the compartment of application and seems not to be metabolized) might be beneficial for further studies to exclude bias by ubiquitous presence and drug elimination. Furthermore, autoradiographic techniques (Solon, 2015) or imaging mass spectrometry (Karlsson and Hanrieder, 2016) might be employed to trace drug entry into the worm and distribution within the worm. Comparison of oral and intravenous application of such compounds might be valuable to elucidate the distribution, delivery to the target parasite and the resulting efficacy.…”