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Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution.

TitleIsotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution.
Publication TypeJournal Article
Year of Publication2016
AuthorsEdgar, LJ, Vellanki, RN, McKee, TD, Hedley, D, Wouters, BG, Nitz, M
JournalAngew Chem Int Ed Engl
Volume55
Issue42
Pagination13159-13163
Date Published2016 10 10
ISSN1521-3773
KeywordsAnimals, Cell Hypoxia, Cell Line, Tumor, Humans, Mice, Molecular Probes, Neoplasms, Experimental, Organometallic Compounds, Tellurium, Tissue Distribution
Abstract

Changes in the oxygenation state of microenvironments within solid tumors are associated with the development of aggressive cancer phenotypes. Factors that influence cellular hypoxia have been characterized; however, methods for measuring the dynamics of oxygenation at a cellular level in vivo have been elusive. We report a series of tellurium-containing isotopologous probes for cellular hypoxia compatible with mass cytometry (MC)-technology that allows for highly parametric interrogation of single cells based on atomic mass spectrometry. Sequential labeling with the isotopologous probes (SLIP) in pancreatic tumor xenograft models revealed changes in cellular oxygenation over time which correlated with the distance from vasculature, the proliferation of cell populations, and proximity to necrosis. SLIP allows for capture of spatial and temporal dynamics in vivo using enzyme activated probes.

DOI10.1002/anie.201607483
Alternate JournalAngew. Chem. Int. Ed. Engl.
PubMed ID27709819