Evaluation of Antiangiogenic Effects of a New Synthetic Candidate Drug KR-31831 on Xenografted Ovarian Carcinoma Using Dynamic Contrast Enhanced MRI.
10.3348/kjr.2011.12.5.602
- Author:
Jehoon YANG
1
;
Jae Hun KIM
;
Geun Ho IM
;
Hyejung HEO
;
Sera YOON
;
Jaewon LEE
;
Jung Hee LEE
;
Pyoung JEON
Author Information
1. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. drpjeon@gmail.com
- Publication Type:Original Article
- Keywords:
Angiogenesis;
Dynamic contrast-enhanced MRI;
Microvascular density;
KR-31831;
VEGF
- MeSH:
Angiogenesis Inhibitors/*pharmacology;
Animals;
Benzopyrans/*pharmacology;
Cell Line, Tumor;
*Contrast Media;
Female;
Humans;
Imidazoles/*pharmacology;
Immunohistochemistry;
*Magnetic Resonance Imaging;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Microvessels/pathology;
Neoplasm Transplantation;
Ovarian Neoplasms/*blood supply/pathology
- From:Korean Journal of Radiology
2011;12(5):602-610
- CountryRepublic of Korea
- Language:English
-
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. MATERIALS AND 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 (Ktrans, ve, and vp) were estimated using a pharmacokinetic model. RESULTS: Qualitatively, the Ktrans parametric mapping showed different changes before and after treatment with KR-31831 in the treatment group. For quantification of this change, the median of Ktrans 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 Ktrans 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). CONCLUSION: 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.
