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Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution
Author(s) -
Edgar Landon J.,
Vellanki Ravi N.,
McKee Trevor D.,
Hedley David,
Wouters Bradly G.,
Nitz Mark
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201607483
Subject(s) - in vivo , mass cytometry , oxygenation , chemistry , hypoxia (environmental) , biophysics , microbiology and biotechnology , flow cytometry , cancer cell , biology , phenotype , biochemistry , cancer , oxygen , ecology , organic chemistry , gene , genetics
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.