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Quantitative contrast-enhanced ultrasound for imaging antiangiogenic treatment response in experimental osteolytic
Maximilian Merz1, Dorde Komljenovic, Wolfhard Semmler
1Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
Objectives:
The aim of this study was to investigate the feasibility of using contrast-enhanced ultrasound (CEUS) in experimental breast cancer bone metastases and its utilization for assessment of early antiangiogenic treatment response in these lesions.
Materials And Methods:
Nude rats bearing bone metastases (n = 20) were treated with the antiangiogenic tyrosine kinase inhibitor sunitinib daily from days 30 to 35 after MDA-MB-231 tumor cell inoculation (n = 10) and compared with sham-treated controls (n = 10). Imaging with ultrasound (US) and magnetic resonance imaging (MRI) was performed on days 30, 32, and 35 after tumor cell inoculation to determine tumor volume and parameters of vascularization in bone metastases. Contrast-enhanced US images were used to calculate wash-in and wash-out values, peak enhancement, and area under the curve from time intensity curves. In addition, a quantitative analysis software was used to determine regional blood volume and flow as well as filling times within bone metastases. For comparison, dynamic contrast-enhanced MRI provided amplitude A and exchange rate constant kep, respectively. Immunohistological analysis of the vasculature in bone metastases followed in vivo imaging experiments.
Results:
Although no changes in tumor volume were assessed in the observation time, significantly decreased values for peak enhancement, area under the curve, and wash-out were determined by CEUS in animals treated with sunitinib at day 35 after tumor cell inoculation. Analysis of CEUS images with quantitative analysis software showed significantly lower values for regional blood volume and regional blood flow as well as higher values for filling time in treated animals as early as 2 days after therapy onset. Dynamic contrast-enhanced MRI revealed significantly decreased values for parameter A at day 35 and kep at days 32 and 35 after tumor cell inoculation for treated animals. Immunohistology of bone metastases revealed significantly larger vessels and decreased positive area fraction for von Willebrand Factor in animals treated with sunitinib.
Conclusion:
Contrast-enhanced US is feasible in experimental breast cancer bone metastases and depicts early antiangiogenic treatment response in advanced osteolytic lesions.
Insights
Contrast-enhanced ultrasound (CEUS) effectively assesses early antiangiogenic treatment response in experimental breast cancer bone metastases. This imaging technique shows changes in vascularization, indicating treatment efficacy in osteolytic lesions.
Area of Science:
- Oncology
- Radiology
- Medical Imaging
Background:
- Breast cancer commonly metastasizes to bone, leading to significant morbidity.
- Assessing early treatment response in bone metastases is crucial for effective patient management.
- Antiangiogenic therapies target tumor vascularization, necessitating imaging techniques to monitor their effects.
Purpose of the Study:
- To evaluate the feasibility of contrast-enhanced ultrasound (CEUS) for imaging experimental breast cancer bone metastases.
- To determine CEUS's utility in assessing early response to antiangiogenic therapy in these lesions.
Main Methods:
- Nude rats with induced breast cancer bone metastases were treated with sunitinib (an antiangiogenic drug) or a sham treatment.
- Ultrasound (US), contrast-enhanced ultrasound (CEUS), and magnetic resonance imaging (MRI) were used to assess tumor volume and vascular parameters.
- Quantitative analysis of CEUS images and immunohistological examination of tumor vasculature were performed.
Main Results:
- CEUS detected significant decreases in peak enhancement, area under the curve, and wash-out in sunitinib-treated animals.
- Quantitative CEUS analysis revealed reduced regional blood volume and flow, and increased filling time, as early as 2 days post-treatment.
- MRI and immunohistology corroborated CEUS findings, showing altered vascular parameters and morphology in treated bone metastases.
Conclusions:
- Contrast-enhanced ultrasound (CEUS) is a feasible imaging modality for experimental breast cancer bone metastases.
- CEUS can effectively depict early antiangiogenic treatment response in advanced osteolytic bone lesions.
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