title: Complex relationship between changes in oxygenation status and changes in R*2: the case of insulin and NS-398, two inhibitors of oxygen consumption.
abstract: Insulin and NS-398 have been reported to inhibit oxygen consumption in experimental tumor models, thereby increasing oxygenation and radiosensitization. The aim of this work was to use MRI to study changes in murine FSaII tumor hemodynamics after administration of those oxygen consumption inhibitors. A multiple-echo gradient-echo (GRE) MRI sequence (4.7 T) was used to map changes in three factors: the GRE signal (at TE=20 ms), the parameter S0 (theoretical signal at TE=0 ms), and the relaxation rate R*2. Perfusion maps were obtained by dynamic contrast-enhanced (DCE) MRI. Insulin caused a significant decrease in the tumor blood oxygen level-dependent (BOLD) signal over time. factor This was likely the result of decreased blood flow, since both S0 and the percentage of perfused tumor decreased as well. Tumor R*2 did not change significantly in response to the treatments, which is surprising considering that other non-MRI techniques (electron paramagnetic resonance (EPR) oximetry and fiber-optic probes) have shown that tumor oxygenation increases after treatment. This suggests that metabolic changes associated with vasoactive challenges may have an unpredictable influence on blood saturation and R*2. In conclusion, this study further emphasizes the fact that changes in BOLD signal and R*2 in tumors do not depend uniquely on changes in oxygenation status.
authors.affiliation: Laboratory of Biomedical Magnetic Resonance, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Crokart
authors.forename: Christine
authors.initials: C
authors.lastname: Baudelet
authors.forename: Greg O
authors.initials: GO
authors.lastname: Cron
authors.forename: Réginald
authors.initials: R
authors.lastname: Ansiaux
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D009578:Nitrobenzenes / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D007328:Insulin; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010100:Oxygen