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Imaging mass spectrometry in drug development and toxicology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2016 (English)In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738Article in journal (Refereed) Epub ahead of print
Abstract [en]

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.

Place, publisher, year, edition, pages
2016.
Keyword [en]
6-OHDA, BMAA, Biologics, L-DOPA, MALDI IMS, Neurotoxicology, Preclinical, SIMS, Small-molecule drugs, Toxins
National Category
Medicinal Chemistry Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-321816DOI: 10.1007/s00204-016-1905-6PubMedID: 27933369OAI: oai:DiVA.org:uu-321816DiVA: diva2:1094899
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2017-05-11

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