title: Exemplifying the Screening Power of Mass Spectrometry Imaging over Label-Based Technologies for Simultaneous Monitoring of Drug and Metabolite Distributions in Tissue Sections.
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.
authors.affiliation: Drug Safety and Metabolism, AstraZeneca R&D, Cambridge, UK richard.goodwin@astrazeneca.com.
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Goodwin
authors.affiliation: Biomolecular Imaging and Proteomics, National Center for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.affiliation: School of Chemistry, University of Edinburgh, Edinburgh, UK.
authors.forename: C Logan
authors.initials: CL
authors.lastname: Mackay
authors.affiliation: Drug Safety and Metabolism, AstraZeneca R&D, Cambridge, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Swales
authors.affiliation: Drug Safety and Metabolism, AstraZeneca R&D, Sweden.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Johansson
authors.affiliation: Drug Safety and Metabolism, AstraZeneca R&D, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Billger
authors.affiliation: Biomolecular Imaging and Proteomics, National Center for Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Per E
authors.initials: PE
authors.lastname: Andrén
authors.affiliation: Drug Safety and Metabolism, AstraZeneca R&D, Sweden.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Iverson
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods; D001812:Blood-Brain Barrier / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D055808:Drug Discovery / Q000379:methods; D008297:Male; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D010455:Peptides; D004364:Pharmaceutical Preparations
keywords: label-free; mass spectrometry imaging; screening