title: Assessment of the interstitial fluid pressure of tumors by dynamic contrast-enhanced magnetic resonance imaging with contrast agents of different molecular weights.
abstract: BACKGROUND
  Cancer patients showing highly elevated interstitial fluid pressure (IFP) in the primary tumor may benefit from particularly aggressive treatment. There is some evidence that gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may be a useful non-invasive method for providing information on the IFP of tumors. The purpose of this preclinical study was to investigate whether any association between DCE-MRI-derived parametric images and tumor IFP can be strengthened by using MR contrast agents with higher molecular weights than that of Gd-DTPA.
  
  
  METHODS
  A-07 human melanoma xenografts were used as preclinical models of human cancer. Three contrast agents were compared: Gd-DTPA (0.55 kDa), P846 (3.5 kDa), and gadomelitol (6.5 kDa). A total of 46 tumors were subjected to DCE-MRI and subsequent measurement of IFP. Parametric images of K(trans) (the volume transfer constant of the contrast agent) and v(e) (the fractional distribution volume of the contrast agent) were produced by pharmacokinetic analysis of the DCE-MRI series.
  
  
  RESULTS
  Significant inverse correlations were found between median K(trans) and IFP for Gd-DTPA (p = 0.0076; R(2) = 0.46; n = 14) and P846 (p = 0.0042; R(2) = 0.45; n = 16), whereas there was no correlation between median K(trans) and IFP for gadomelitol (p > 0.05; n = 16). Significant correlation between median v(e) and IFP was not found for any of the contrast agents (p > 0.05 for Gd-DTPA, P846, and gadomelitol).
  
  
  CONCLUSIONS
  K(trans) images, but not v(e) images, derived by pharmacokinetic analysis of DCE-MRI data for low-molecular-weight contrast agents may provide information on the IFP of tumors. Any association between K(trans) and IFP cannot be expected to be improved by using contrast agents with higher molecular weights than those of Gd-DTPA and P846.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Tord
authors.initials: T
authors.lastname: Hompland
authors.forename: Kristine
authors.initials: K
authors.lastname: Gulliksrud
authors.forename: Christine
authors.initials: C
authors.lastname: Ellingsen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D045604:Extracellular Fluid; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008970:Molecular Weight; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011312:Pressure; D011859:Radiography; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA