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.

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 (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).

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.

• Authors: Jehoon Yang, Jae-Hun Kim, Geun-Ho Im, Hyejung Heo, Sera Yoon, Jaewon Lee, Jung Hee Lee, Pyoung Jeon
• Journal: Korean journal of radiology (Korean J Radiol) 2011 Sep-Oct Vol. 12 Issue 5 Pg. 602-10 ISSN: 2005-8330 [Electronic] Korea (South)
• PMID: 21927562 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Benzopyrans
• Contrast Media
• Imidazoles
• KR 31831

Topics

• 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)