title: In vivo measurement of tissue oxygenation by time-resolved luminescence spectroscopy: advantageous properties of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate.
abstract: Measuring tissue oxygenation in vivo is of interest in fundamental biological as well as medical applications. One minimally invasive approach to assess the oxygen partial pressure in tissue (pO2) is to measure the oxygen-dependent luminescence lifetime of molecular probes. The relation between tissue pO2 and the probes’ luminescence lifetime is governed by the Stern-Volmer equation. Unfortunately, virtually all oxygen-sensitive probes based on this principle induce some degree of phototoxicity. For that reason, we studied the oxygen sensitivity and phototoxicity of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate [Ru(Phen)] using a dedicated optical fiber–based, time-resolved spectrometer in the chicken embryo chorioallantoic membrane. We demonstrated that, after intravenous injection, Ru(Phen)’s luminescence lifetime presents an easily detectable pO2 dependence at a low drug dose (1 mg∕kg) and low fluence (120 mJ∕cm2 at 470 nm). The phototoxic threshold was found to be at 10 J∕cm2 with the same wavelength and drug dose, i.e., about two orders of magnitude larger than the fluence necessary to perform a pO2 measurement. Finally, an illustrative application of this pO2 measurement approach in a hypoxic tumor environment is presented.
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, Switzerland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Huntosova
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gay
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, SwitzerlandbUniversity Hospital (CHUV), Department of Urology, BH-10, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Nowak-Sliwinska
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, Switzerland.
authors.forename: Senthil Kumar
authors.initials: SK
authors.lastname: Rajendran
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, Switzerland.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Zellweger
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, Switzerland.
authors.forename: Hubert
authors.initials: H
authors.lastname: van den Bergh
authors.affiliation: Swiss Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering, Station 6, CH-1015 Lausanne, Switzerland.
authors.forename: Georges
authors.initials: G
authors.lastname: Wagnières
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D009374:Neoplasms, Experimental; D055100:Optical Fibers; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D010100:Oxygen / Q000032:analysis*; D010313:Partial Pressure; D010618:Phenanthrolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D012428:Ruthenium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D010618:Phenanthrolines; D012428:Ruthenium; D010100:Oxygen