title: Assessment of fraction of radiobiologically hypoxic cells in human melanoma xenografts by dynamic contrast-enhanced MRI.
abstract: A noninvasive method for assessment of the extent of hypoxia in experimental and human tumors is highly needed. In this study, the potential usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was investigated, using gadopentetate dimeglumine (Gd-DTPA) as contrast agent and A-07 human melanoma xenografts as tumor model. DCE-MRI was performed at a voxel size of 0.3 x 0.6 x 2.0 mm3 with spoiled gradient-recalled sequences. Images of E . F (E is the initial extraction fraction of Gd-DTPA and F is perfusion) and lambda (the partition coefficient of Gd-DTPA, which is proportional to extracellular volume fraction) were obtained by Kety analysis of DCE-MRI data. The study was based on the hypothesis that hypoxic tissue would have low E . F (i.e., poor oxygen supply) and/or low lambda (i.e., high cell density and, hence, high oxygen consumption rate). Twenty-two tumors were first subjected to DCE-MRI and then to measurement of fraction of hypoxic cells, using a radiobiological assay. E . F was found to be strongly correlated to fraction of hypoxic cells (P < 0.000001), whereas significant correlation between lambda and fraction of hypoxic cells could not be detected. It is thus possible that E . F may be a useful parameter for the extent of hypoxia in experimental and human tumors with physiologic properties similar to those of A-07 tumors. This possibility warrants further studies involving experimental tumors of several lines, as well as human tumors.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
authors.forename: Tormod A M
authors.initials: TA
authors.lastname: Egeland
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.forename: Ida K
authors.initials: IK
authors.lastname: Vestvik
authors.forename: Ilana C
authors.initials: IC
authors.lastname: Benjaminsen
authors.forename: Berit
authors.initials: B
authors.lastname: Mathiesen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006801:Humans; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008546:Melanoma, Experimental / Q000098:blood supply*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA