Contrast-enhanced Ultrasound Imaging of Antiangiogenic Tumor Therapy
Laura V Klotz1, Dirk-Andre Clevert2, Siiri Scheckinger3
1Clinic of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany Walter-Brendel-Centre of Experimental Medicine, University of Munich, Munich, Germany Laura.Klotz@med.uni-muenchen.de.
Background/Aim:
Anti-angiogenic treatment is a promising strategy for cancer therapy and is currently evaluated in clinical trials. The aim of the present study was to further investigate the effects of an anti-angiogenic therapy, inhibiting vascular endothelial growth factor (VEGF) and endothelial growth factor (EGF) using a tyrosine kinase inhibitor for blocking tumor angiogenesis and tumor progression in vivo.
Materials And Methods:
Experiments were performed using C57/Bl6 mice (25 ± 5 g of body weight (b.w.)) implanted with subcutaneous Lewis lung carcinoma (LLC-1). From day 7 till 21 after tumor cell implantation, animals (n=7 per group) were treated by monotherapy using ZD6474 (50 mg/kg b.w. per os (p.o.)) daily. A control group received only the solvent polysorbate 80. Using contrast enhanced ultrasound (CE-US) parameters of intra-tumoral microcirculation animals were examined 24 h after the last application of ZD6474. Moreover, subcutaneous tumor growth was measured over the whole therapy period. Finally, histological analyses were performed to analyze the functional vessel density in the tumor tissue.
Results:
ZD6474 reduced tumor growth of LLC-1 in C57/Bl6 mice significantly. A significant difference of maximal signal intensity (ΔSImax) and area below the intensity time curve (AUC) after antiangiogenic therapy was recorded in the tumor center by CE-US. Vessel density after hematoxyline and eosin, as well as CD31, staining showed no significant difference in both groups.
Conclusion:
Anti-angiogenic effects can be quantitatively demonstrated using CE-US imaging, which represents the spreading of efficient vessels in the tumor tissue, especially in the tumor center.
Insights
This study shows that ZD6474, an anti-angiogenic therapy, effectively reduces tumor growth by impacting tumor microcirculation. Contrast-enhanced ultrasound (CE-US) can quantitatively assess these anti-angiogenic effects in vivo.
Area of Science:
- Oncology
- Pharmacology
- Medical Imaging
Background:
- Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are promising cancer treatments.
- Tyrosine kinase inhibitors are being evaluated for their potential to block tumor angiogenesis and progression.
Purpose of the Study:
- To investigate the in vivo effects of the tyrosine kinase inhibitor ZD6474 on tumor angiogenesis and progression.
- To evaluate the efficacy of ZD6474 in inhibiting tumor growth and altering intra-tumoral microcirculation.
Main Methods:
- C57/Bl6 mice with subcutaneous Lewis lung carcinoma (LLC-1) were treated daily with ZD6474 (50 mg/kg) or vehicle control from day 7 to 21.
- Contrast-enhanced ultrasound (CE-US) was used to assess intra-tumoral microcirculation 24 hours after the last treatment.
- Tumor growth was measured, and histological analyses (H&E, CD31 staining) were performed to evaluate vessel density.
Main Results:
- ZD6474 significantly reduced LLC-1 tumor growth in mice.
- CE-US revealed significant differences in maximal signal intensity (ΔSImax) and area under the curve (AUC) in the tumor center after ZD6474 treatment.
- No significant differences in functional vessel density were observed between the ZD6474 and control groups via histological analysis.
Conclusions:
- Anti-angiogenic therapy with ZD6474 effectively inhibits tumor growth and impacts tumor microcirculation.
- CE-US imaging provides a quantitative method to demonstrate anti-angiogenic effects, particularly in the tumor center.
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