title: Evaluation of antiangiogenic effects of a new synthetic candidate drug KR-31831 on xenografted ovarian carcinoma using dynamic contrast enhanced MRI.
abstract: OBJECTIVE
  The purpose of this research was to investigate the anti-angiogenic inhibitory effect of KR-31831, a newly developed anti-angiogenic agent, on an in vivo human ovarian carcinoma model using dynamic contrast-enhanced (DCE) MRI.
  
  
  METHODS
  Xenografted ovarian tumors were established by subcutaneous injection of SKOV3 cells into mice. The mice were treated daily with KR-31831 at 50 mg/kg for 21 days. Tumor tissues were excised corresponding to the DCE-MRI sections for evaluation of MVD with CD31 immunohistochemistry. All in vivo MRIs were performed on a 7.0 Tesla micro-MRI System. DCE-MRI was acquired prior to initiating treatment with KR-31831 and again on days 3 and 21 after treatment. The permeability parameters (K(trans), v(e), and v(p)) were estimated using a pharmacokinetic model.
  
  
  RESULTS
  Qualitatively, the K(trans) parametric mapping showed different changes before and after treatment with KR-31831 in the treatment group. For quantification of this change, the median of K(trans) values were compared before and after treatments in the control and KR-31831-treated groups. A non-parametric statistical test (Wilcoxon signed-rank test) showed decreasing K(trans) values on day 21 compared to days 0 and 3 in the KR-31831-treated group (p < 0.05), whereas there was no significant difference in the control group (p = 0.84).
  
  
  CONCLUSIONS
  Our results suggest that DCE-MRI can be a useful tool by which to evaluate the anti-angiogenic effect of KR-31831 on a xenografted human ovarian carcinoma model.
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors.forename: Jehoon
authors.initials: J
authors.lastname: Yang
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Geun-Ho
authors.initials: GH
authors.lastname: Im
authors.forename: Hyejung
authors.initials: H
authors.lastname: Heo
authors.forename: Sera
authors.initials: S
authors.lastname: Yoon
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Pyoung
authors.initials: P
authors.lastname: Jeon
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D001578:Benzopyrans; D003287:Contrast Media; D007093:Imidazoles; C503693:KR 31831