title: Dynamic contrast-enhanced-MRI of tumor hypoxia.
abstract: Patients with highly hypoxic primary tumors show increased frequency of locoregional treatment failure and poor survival rates and may benefit from particularly aggressive treatment. The potential of gadolinium diethylene-triamine penta-acetic acid-based dynamic contrast-enhanced-MRI in assessing tumor hypoxia was investigated in this preclinical study. Xenografted tumors of eight human melanoma lines were subjected to dynamic contrast-enhanced-MRI and measurement of the fraction of radiobiologically hypoxic cells and the fraction of pimonidazole-positive hypoxic cells. Tumor images of K(trans) (the volume transfer constant of gadolinium diethylene-triamine penta-acetic acid) and v(e) (the fractional distribution volume of gadolinium diethylene-triamine penta-acetic acid) were produced by pharmacokinetic analysis of the dynamic contrast-enhanced-MRI data, and K(trans) and v(e) frequency distributions of the non-necrotic tumor tissue were established and related to the extent of hypoxia. Tumors showing high K(trans) values and high v(e) values had low fractions of hypoxic cells, whereas tumors showing both low K(trans) values and low v(e) values had high hypoxic fractions. K(trans) differentiated better between tumors with low and high hypoxic fractions than did v(e). This study supports the current attempts to establish dynamic contrast-enhanced-MRI as a method for assessing the extent of hypoxia in human tumors, and it provides guidelines for the clinical development of valid assays.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Tormod A M
authors.initials: TA
authors.lastname: Egeland
authors.forename: Kristine
authors.initials: K
authors.lastname: Gulliksrud
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.forename: Berit
authors.initials: B
authors.lastname: Mathiesen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009593:Nitroimidazoles / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000032:analysis; D012680:Sensitivity and Specificity; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D003287:Contrast Media; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D019786:Gadolinium DTPA