Evaluation of Antiangiogenic Effects of a New Synthetic Candidate Drug KR-31831 on Xenografted Ovarian Carcinoma Using Dynamic Contrast Enhanced MRI

Abstract

ObjectiveThe 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 MethodsXenografted 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.ResultsQualitatively, 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).ConclusionOur 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.

Semiquantitative dynamic contrast-enhanced MRI for accurate classification of complex adnexal masses

“…The relationships of these two parameters with physiological biomarkers of ovarian tumor malignancy have been confirmed previously . The relevance of these two parameters to the pathophysiological properties of tumors can be explained by the highly permeable tumor neovasculature that is aggravated when the tumor advances into a malignant form . Therefore, by inspecting DCE‐MRI curves in malignant lesions, a steep slope of enhancement, ie, higher wash‐in‐rate and smaller initial time to enhancement peak, denoting the time by which the contrast agent has permeated into the microvasculature, can be observed.…”

“…5,7,21 The relevance of these two parameters to the pathophysiological properties of tumors can be explained by the highly permeable tumor neovasculature that is aggravated when the tumor advances into a malignant form. 22 Therefore, by inspecting DCE-MRI curves in malignant lesions, a steep slope of enhancement, ie, higher wash-in-rate and smaller initial time to enhancement peak, denoting the time by which the contrast agent has permeated into the microvasculature, can be observed. This finding is consistent with several related studies where WIR and/or TTP (with other equivalent terminologies) have been reported as helpful indicators for discriminating benign and malignant ovarian masses.…”

Correlation of quantitative dynamic contrast‐enhanced MRI with microvascular density in necrotic, partial necrotic, and viable liver tumors in a rabbit model

“…DCE‐MRI has recently been used to monitor therapeutic responses to new treatment methods and to evaluate the effects of new antiangiogenic drugs in preclinical and clinical studies 3 , 4 , 5 , 6 , 7 …”

Preliminary Experience Using Dynamic MRI at 3.0 Tesla for Evaluation of Soft Tissue Tumors

“…Also, it is not clear whether it is appropriate to include vascular tumors, such as hemangiomas in the benign tumor group. Further research using various parametric imaging techniques that are less reliant on ROI areas and 3D sequences covering the whole tumor may overcome these deficiencies, while further correlation with quantitative pharmacokinetic DCE-MRI parameters is also warranted (15-18). Lastly, one must be careful when comparing DCE-MRI study results as dynamic MRI examinations from different measurement conditions or scanners are difficult to compare with each other (19).…”