title: Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution.
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.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.
authors.forename: Landon J
authors.initials: LJ
authors.lastname: Edgar
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, and the, STTARR Innovaton Centre, Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Ravi N
authors.initials: RN
authors.lastname: Vellanki
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, and the, STTARR Innovaton Centre, Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: McKee
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, and the, STTARR Innovaton Centre, Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.affiliation: Departments of Radiation Oncology, Medical Biophysics, and the, STTARR Innovaton Centre, Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Bradly G
authors.initials: BG
authors.lastname: Wouters
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada. mnitz@chem.utoronto.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Nitz
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013691:Tellurium / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D015335:Molecular Probes; D009942:Organometallic Compounds; D013691:Tellurium
keywords: activity-based probes; cellular hypoxia; dynamic biology; mass spectrometry; tellurium