title: 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.
authors.affiliation: Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden. oskar.karlsson@ki.se.|Department of Pharmaceutical Biosciences, Drug Safety and Toxicology, Uppsala University, 751 24, Uppsala, Sweden. oskar.karlsson@ki.se.
authors.forename: Oskar
authors.initials: O
authors.lastname: Karlsson
authors.affiliation: Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal Hospital, House V, 431 80, Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London, WC1N, UK.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hanrieder
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055808:Drug Discovery / Q000295:instrumentation* / Q000379:methods; D015507:Drugs, Investigational / Q000493:pharmacokinetics / Q000633:toxicity; D015386:Hazardous Substances / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D007091:Image Processing, Computer-Assisted; D057054:Molecular Imaging / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods; D014018:Tissue Distribution; D014116:Toxicology / Q000295:instrumentation* / Q000379:methods
chemical_list: D015415:Biomarkers; D015507:Drugs, Investigational; D015386:Hazardous Substances
keywords: 6-OHDA; BMAA; Biologics; L-DOPA; MALDI IMS; Neurotoxicology; Preclinical; SIMS; Small-molecule drugs; Toxins