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Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging

Liu, XH and Ide, JL and Norton, I and Marchionni, MA and Ebling, MC and Wang, LY and Davis, E and Sauvageot, CM and Kesari, S and Kellersberger, KA and Easterling, ML and Santagata, S and Stuart, DD and Alberta, J and Agar, JN and Stiles, CD and Agar, NYR (2013) Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Scientific Reports.

Abstract

Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain - insights that would be difficult or impossible to extract by use of radiolabeled compounds

Item Type: Article
Additional Information: pubid: 149 nvp_institute: NIBR contributor_address: [Liu, Xiaohui; Ide, Jennifer L.; Norton, Isaiah; Ebling, Maritza C.; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Marchionni, Mark A.; Wang, Lan Y.; Davis, Erin; Sauvageot, Claire M.; Alberta, John; Stiles, Charles D.; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kesari, Santosh] Univ Calif San Diego, La Jolla, CA 92093 USA. [Kellersberger, Katherine A.; Easterling, Michael L.] Bruker Daltonics Inc, Billerica, MA USA. [Santagata, Sandro] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stuart, Darrin D.] Novartis Inst BioMed Res, Emeryville, CA USA. [Agar, Jeffrey N.] Brandeis Univ, Waltham, MA USA. [Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/21981

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