Volumetric high-frequency Doppler ultrasound enables the assessment of early antiangiogenic therapy effects on tumor xenografts in nude mice
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The sensitivity of Doppler ultrasound below 10 MHz to assess antiangiogenic therapy effects in tumor xenografts has been shown to be limited. Thus, our aim was to evaluate high-frequency volumetric power-Doppler ultrasound (HF-VPDU) for monitoring antiangiogenic treatments. Squamous cell carcinoma xenografts grown in nude mice were scanned with HF-VPDU at a center frequency of 30 MHz. Images with 200-μm slice thicknesses were recorded and merged into a three-dimensional dataset, of which the relative color pixel density was determined. Animals received either VEGFR2 antibodies or 0.9% NaCl and were examined at days 0, 3 and 6 of treatment. After the last examination, tumors were resected and their vascularization characterized by immunohistology. At day 6, the volumes of treated and untreated tumors were not significantly different yet. In contrast, mean tumor vascularization in treated animals had decreased to 44%, while in the control group it had increased to 152% (P < 0.01). In correspondence, vessel density, as determined by CD31 staining, was 0.19 ± 0.10% in treated and 0.92 ± 0.41% in untreated tumors (P < 0.01). Additionally, the fraction of mature (SMA-positive) vessels increased under therapy. Thus, HF-VPDU can be considered as an easily applicable and fast method to screen high animal numbers for antiangiogenic therapy effects.
KeywordsAngiogenesis Tumor therapy Ultrasound High frequency Power Doppler
This work was supported by the transregional grant Vascular differentiation and remodeling from the German Research Foundation (DFG, SFB-TR23).
- 2.Folkman J (2003) Angiogenesis inhibitors: a new class of drugs. Cancer Biol Ther 2:127–133Google Scholar
- 4.Kiessling F, Farhan N, Lichy MP, Vosseler S, Heilmann M, Krix M, Bohlen P, Miller DW, Mueller MM, Semmler W, Fusenig NE, Delorme S (2004) Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101. Neoplasia 6:213–223PubMedCrossRefGoogle Scholar
- 16.Mueller MM, Peter W, Mappes M, Huelsen A, Steinbauer H, Boukamp P, Vaccariello M, Garlick J, Fusenig NE (2001) Tumor progression of skin carcinoma cells in vivo promoted by clonal selection, mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Am J Pathol 159:1567–1579PubMedGoogle Scholar