title: Phosphorescent ruthenium complexes with a nitroimidazole unit that image oxygen fluctuation in tumor tissue.
abstract: Understanding oxygen fluctuation in a cancerous tumor is important for effective treatment, especially during radiotherapy. In this paper, ruthenium complexes bearing a nitroimidazole group are shown to report the oxygen status in tumor tissue directly. The nitroimidazole group was known to be accumulated in hypoxic tumor tissues. On the other hand, the ruthenium complex showed strong phosphorescence around 600 nm. The emission of ruthenium is quenched instantaneously by molecular oxygen due to energy transfer between triplet states of oxygen and ruthenium complex, but the emission is then recovered by the removal of oxygen. Thus, we could observe oxygen fluctuation in tumor tissue in a real-time manner by monitoring the phosphorescence of the ruthenium complex. The versatility of the probe is demonstrated by monitoring oxygen fluctuation in living cells and tumor tissue planted in mice. The ruthenium complex promptly penetrated plasma membrane and accumulated in cells to emit its oxygen-dependent phosphorescence. In vivo experiments revealed that the oxygen level in tumor tissue seems to fluctuate at the sub-minute timescale.
authors.affiliation: Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504.
authors.forename: Aoi
authors.initials: A
authors.lastname: Son
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Daiki
authors.initials: D
authors.lastname: Hara
authors.forename: Takeo
authors.initials: T
authors.lastname: Ito
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004735:Energy Transfer; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009593:Nitroimidazoles / Q000737:chemistry*; D061848:Optical Imaging; D010100:Oxygen / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D056831:Coordination Complexes; D009593:Nitroimidazoles; D049452:Green Fluorescent Proteins; D012428:Ruthenium; D010100:Oxygen
keywords: molecular imaging; oxygen; phosphorescence; ruthenium; tumors