Exemplifying the Screening Power of Mass Spectrometry Imaging over Label-Based Technologies for Simultaneous Monitoring of Drug and Metabolite Distributions in Tissue Sections

Mass spectrometry imaging (MSI) provides pharmaceutical researchers with a suite of technologies to screen and assess compound distributions and relative abundances directly from tissue sections and offer insight into drug discovery-applicable queries such as blood-brain barrier access, tumor penetr...

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Bibliographic Details
Published inJournal of biomolecular screening Vol. 21; no. 2; pp. 187 - 193
Main Authors Goodwin, Richard J A, Nilsson, Anna, Mackay, C Logan, Swales, John G, Johansson, Maria K, Billger, Martin, Andrén, Per E, Iverson, Suzanne L
Format Journal Article
LanguageEnglish
Published United States 01.02.2016
Subjects
Animals
Autoradiography - methods
Blood-Brain Barrier - metabolism
Diagnostic Imaging - methods
Drug Discovery - methods
Male
Mice, Inbred C57BL
Neoplasms - metabolism
Peptides - metabolism
Pharmaceutical Preparations - metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
mass spectrometry imaging
label-free
screening
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Summary:Mass spectrometry imaging (MSI) provides pharmaceutical researchers with a suite of technologies to screen and assess compound distributions and relative abundances directly from tissue sections and offer insight into drug discovery-applicable queries such as blood-brain barrier access, tumor penetration/retention, and compound toxicity related to drug retention in specific organs/cell types. Label-free MSI offers advantages over label-based assays, such as quantitative whole-body autoradiography (QWBA), in the ability to simultaneously differentiate and monitor both drug and drug metabolites. Such discrimination is not possible by label-based assays if a drug metabolite still contains the radiolabel. Here, we present data exemplifying the advantages of MSI analysis. Data of the distribution of AZD2820, a therapeutic cyclic peptide, are related to corresponding QWBA data. Distribution of AZD2820 and two metabolites is achieved by MSI, which [(14)C]AZD2820 QWBA fails to differentiate. Furthermore, the high mass-resolving power of Fourier transform ion cyclotron resonance MS is used to separate closely associated ions.
ISSN:2472-5552
1552-454X
DOI:10.1177/1087057115623740