title: Tissue redox activity as a sensing platform for imaging of cancer based on nitroxide redox cycle.
abstract: The experience in free radical biology and medicine shows the crucial role of redox signalling in carcinogenesis. The cells and tissues of healthy mammals are characterised by a low level of reactive oxygen species (ROS) and some constant (reference) level of reducing equivalents. Increasing of ROS above the critical level provokes genomic instability. The present study describes universal methodology for direct imaging of tissue redox activity in carcinogenesis, which allows a differentiation of cancer development from normal condition. The experiments were conducted on: neuroblastoma-bearing mice; colon cancer-bearing mice; and healthy mice. The tissue redox activity was visualised in vivo by nitroxide-enhanced magnetic resonance imaging (MRI) on anesthetised animals. The method is based on nitroxide redox cycle, coupled with appearance/disappearance of MRI signal. The half-life (τ1/2) of nitroxide-enhanced MRI signal in the respective tissue was used as a diagnostic marker. The study provides direct evidence that healthy and cancer-bearing mammalian tissues are characterised by different redox activities - a basis for cancer diagnosis. The tissues (cancer and 'normal') of cancer-bearing mammals were characterised by a long-lived MRI signal (τ1/2>14 min), indicating a high oxidative activity. The tissues of healthy organism were characterised by a short-lived MRI signal (τ1/2=1-3 min), indicating a high reducing activity. The study shows that tissue redox activity is a sensing platform for imaging of cancer using nitroxide-enhanced MRI. It also suggests that 'normal' tissues of cancer-bearing organism are susceptible to oxidative damage.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city 263-8555, Japan.
authors.forename: Zhivko
authors.initials: Z
authors.lastname: Zhelev
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.forename: Veselina
authors.initials: V
authors.lastname: Gadjeva
authors.forename: Biliana
authors.initials: B
authors.lastname: Nikolova
authors.forename: Rumiana
authors.initials: R
authors.lastname: Bakalova
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006614:Hindlimb / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008956:Models, Chemical; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009589:Nitrogen Oxides / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013997:Time Factors
chemical_list: D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; C039900:nitroxyl