Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution

• Published in: Angewandte Chemie Vol. 128; no. 42; pp. 13353 - 13357
• Main Authors: Edgar, Landon J., Vellanki, Ravi N., McKee, Trevor D., Hedley, David, Wouters, Bradly G., Nitz, Mark
• Format: Journal Article
• Language: English
• Published: Weinheim Blackwell Publishing Ltd 10.10.2016; Wiley Subscription Services, Inc
• Subjects: Aktivitätsbasierte Sonden; Atomic properties; Cancer; Chemistry; Compatibility; Correlation; Cytometry; Dynamics; Dynamische Biologie; Enzymes; Hypoxia; Interrogation; Labels; Marking; Mass spectrometry; Mass spectroscopy; Massenspektrometrie; Mathematical models; Measurement methods; Microenvironments; Necrosis; Oxygenation; Pancreas; Populations; Probes; Proximity; Slip; Solid tumors; Spatial analysis; Technology; Tellur; Tellurium; Tumors; Xenografts; Zelluläre Hypoxie
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201607483

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. Sauerstoff auf dem Schirm: Der Einbau von isotopenangereichertem Tellur in ein biokompatibles Tellurophen ermöglichte die Herstellung einer Serie von analytisch unterscheidbaren, aber pharmakologisch identischen aktivitätsbasierten Sonden zellulärer Hypoxie. Durch serielle Injektion der isotopologen Sonden in Mäuse mit humanen Tumoren konnte die Dynamik der zellulären Hypoxie mittels bildgebender Massenzytometrie visualisiert werden.