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2017 ; 91
(6
): 2283-2294
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Imaging mass spectrometry in drug development and toxicology
#MMPMID27933369
Karlsson O
; Hanrieder J
Arch Toxicol
2017[Jun]; 91
(6
): 2283-2294
PMID27933369
show ga
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.