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Exemplifying the Screening Power of Mass Spectrometry Imaging over Label-Based Technologies for Simultaneous Monitoring of Drug and Metabolite Distributions in Tissue Sections
AstraZeneca R&D, Drug Safety & Metab, Cambridge CB4 OWG, England..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Univ Edinburgh, Sch Chem, Edinburgh, Midlothian, Scotland..
AstraZeneca R&D, Drug Safety & Metab, Cambridge CB4 OWG, England..
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2016 (English)In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 21, no 2, 187-193 p.Article in journal (Refereed) Published
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Abstract [en]

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 [C-14] 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.

Place, publisher, year, edition, pages
2016. Vol. 21, no 2, 187-193 p.
Keyword [en]
label-free, mass spectrometry imaging, screening
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-276793DOI: 10.1177/1087057115623740ISI: 000368325000010PubMedID: 26701101OAI: oai:DiVA.org:uu-276793DiVA: diva2:903585
Funder
Swedish Research Council, 2013-3105Swedish Research Council, 2014-6215Swedish Research Council, 2009-6050
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2017-11-30Bibliographically approved

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Nilsson, AnnaAndrén, Per E.

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Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Radiology, Nuclear Medicine and Medical Imaging

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