title: Assessment of tumor hypoxia and interstitial fluid pressure by gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging.
abstract: OBJECTIVE
  Extensive hypoxia and high interstitial fluid pressure (IFP) in the primary tumor may cause resistance to radiation treatment and promote metastatic spread. The potential of gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the extent of hypoxia and the level of interstitial hypertension in tumors was investigated in this preclinical study.
  
  
  METHODS
  Twenty-three A-07 tumors were subjected to DCE-MRI and subsequent measurement of IFP and fraction of pimonidazole-positive hypoxic tissue (HF(Pim)). Parametric tumor images of K(trans), v(e), and V(b)(Tofts) (Tofts model) and of K(i) and V(b)(Patlak) (Patlak model) were produced by pharmacokinetic analyses of the DCE-MRI series.
  
  
  RESULTS
  There was no correlation between IFP and HF(Pim) in the tumors. K(trans) and K(i) decreased significantly with increasing HF(Pim), whereas V(b)(Tofts) and V(b)(Patlak) increased significantly with increasing IFP.
  
  
  CONCLUSIONS
  Information on both the extent of hypoxia and the level of interstitial hypertension in A-07 tumors can be derived from a single DCE-MRI series by using gadomelitol as contrast agent.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
authors.forename: Kristine
authors.initials: K
authors.lastname: Gulliksrud
authors.forename: Tord
authors.initials: T
authors.lastname: Hompland
authors.forename: Kanthi
authors.initials: K
authors.lastname: Galappathi
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D004195:Disease Models, Animal; D045604:Extracellular Fluid / Q000187:drug effects; D005260:Female; D019786:Gadolinium DTPA / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011312:Pressure; D011897:Random Allocation; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis*
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA