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Published on: September 11, 2013
Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging
Stefan Zwick1, Ralph Strecker, Valerji Kiselev
1Siemens AG, Healthcare Sector, Erlangen, Germany. s.zwick@dkfz.de
Purpose:
To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response.
Materials And Methods:
In two independent experiments, nude mice bearing human skin squamous cell carcinoma xenografts were treated with a vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248). Changes in tumor vascularity were assessed by DCE-MRI and vessel size imaging. DCE-MRI data were analyzed applying a two-compartment model (Brix), calculating the parameters Amplitude and k(ep).
Results:
For both experiments Amplitude decreased significantly in treated tumors while k(ep) did not change significantly. VSI showed controversial results. VSI was significantly increased in SU11248-treated A431 tumors, whereas no changes were found in bevacizumab-treated HaCaT-ras-A-5RT3 tumors. Immunohistology confirmed these results and suggest differences in the maturation of tumor vascularization as a possible explanation.
Conclusion:
DCE-MRI and vessel size imaging provide reliable and supplementing biomarkers of antiangiogenic therapy response. The results of both methods are in excellent agreement with histology. Nevertheless, our results also indicate that vascular remodeling is complex and that a uniform response cannot be expected for different tumors and therapies.
Insights
Dynamic contrast-enhanced MRI (DCE-MRI) and vessel size imaging show promise as biomarkers for anti-angiogenic therapy response. However, tumor vascular remodeling is complex and varies between therapies and tumor types.
Area of Science:
- Oncology
- Radiology
- Biomarkers
Background:
- Anti-angiogenic therapies are crucial in cancer treatment.
- Assessing treatment response requires reliable imaging biomarkers.
- Tumor vascular remodeling is a key factor in therapy efficacy.
Purpose of the Study:
- To evaluate vascular remodeling in tumors under two anti-angiogenic treatments using DCE-MRI and vessel size imaging.
- To assess the vessel size index (VSI) as a novel biomarker for anti-angiogenic therapy response.
- To compare imaging findings with histological data.
Main Methods:
- Nude mice bearing human skin squamous cell carcinoma xenografts were treated with bevacizumab or SU11248.
- Tumor vascularity was assessed using DCE-MRI and vessel size imaging.
- DCE-MRI data were analyzed with a two-compartment model (Brix), calculating Amplitude and k(ep).
Main Results:
- Tumor Amplitude significantly decreased with both therapies; k(ep) showed no significant change.
- VSI results were controversial: increased with SU11248, but unchanged with bevacizumab.
- Immunohistology supported imaging findings, suggesting differences in vascular maturation.
Conclusions:
- DCE-MRI and vessel size imaging offer reliable, complementary biomarkers for anti-angiogenic therapy response.
- Imaging results correlate well with histological findings.
- Tumor vascular remodeling is complex, with varied responses expected across different tumors and therapies.
