title: Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure.
abstract: BACKGROUND
  High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI.
  
  
  METHODS
  CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm³ and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model.
  
  
  RESULTS
  When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent.
  
  
  CONCLUSIONS
  Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, Box 4953, Oslo N-0424, Norway.
authors.forename: Tord
authors.initials: T
authors.lastname: Hompland
authors.forename: Christine
authors.initials: C
authors.lastname: Ellingsen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D003287:Contrast Media / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D045604:Extracellular Fluid / Q000502:physiology*; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds; D011312:Pressure; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D019786:Gadolinium DTPA; C435266:contrast agent P792