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

Richard J A Goodwin, Anna Nilsson, C Logan Mackay, John G Swales, Maria K Johansson, Martin Billger, Per E Andrén, Suzanne L Iverson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)187-93
Number of pages7
JournalJournal of Biomolecular Screening
Volume21
Issue number2
Early online date23 Dec 2015
DOIs
Publication statusPublished - 1 Feb 2016

Keywords

  • Animals
  • Autoradiography
  • Blood-Brain Barrier
  • Diagnostic Imaging
  • Drug Discovery
  • Male
  • Mice, Inbred C57BL
  • Neoplasms
  • Peptides
  • Pharmaceutical Preparations
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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