title: Assessment of hypoxia and radiation response in intramuscular experimental tumors by dynamic contrast-enhanced magnetic resonance imaging.
abstract: OBJECTIVE
  Studies of intradermal melanoma xenografts have suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may be a useful method for assessing the extent of hypoxia in tumors. Because the microvascular network of tumors is influenced significantly by the site of growth, we challenged this possibility in the present work by studying relationships between DCE-MRI-derived parameters and hypoxia in intramuscular melanoma xenografts.
  
  
  METHODS
  Intramuscular R-18, U-25, and V-27 tumors were subjected to DCE-MRI and measurement of the fraction of radiobiologically hypoxic cells (HF(Rad)). Parametric images of K(trans) and v(e) were produced by pharmacokinetic analysis, and K(trans) and v(e) were related to HF(Rad) in individual tumors.
  
  
  RESULTS
  K(trans) decreased with increasing HF(Rad). The correlations between K(trans) and HF(Rad) were similar for the three tumor lines and were highly significant (P<0.00001). There was no correlation between v(e) and HF(Rad). However, v(e) decreased significantly with increasing cell survival after single dose irradiation.
  
  
  CONCLUSIONS
  Intramuscular melanoma xenografts show similar inverse correlations between K(trans) and HF(Rad) as intradermal tumors, which support the current clinical attempts to establish DCE-MRI as a method for detecting hypoxia and defining therapeutic targets in tumors.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
authors.forename: Kirsti Marie
authors.initials: KM
authors.lastname: Øvrebø
authors.forename: Tord
authors.initials: T
authors.lastname: Hompland
authors.forename: Berit
authors.initials: B
authors.lastname: Mathiesen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000328:Adult; D000818:Animals; D003287:Contrast Media; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis*; D007089:Image Enhancement; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008546:Melanoma, Experimental / Q000175:diagnosis / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011836:Radiation Tolerance
chemical_list: D003287:Contrast Media