European Radiology

, Volume 18, Issue 4, pp 753–758 | Cite as

Volumetric high-frequency Doppler ultrasound enables the assessment of early antiangiogenic therapy effects on tumor xenografts in nude mice

  • Manfred Jugold
  • Moritz Palmowski
  • Jochen Huppert
  • Eva C. Woenne
  • Margareta M. Mueller
  • Wolfhard Semmler
  • Fabian Kiessling
Molecular Imaging

Abstract

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.

Keywords

Angiogenesis Tumor therapy Ultrasound High frequency Power Doppler 

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Copyright information

© European Society of Radiology 2007

Authors and Affiliations

  • Manfred Jugold
    • 1
    • 2
  • Moritz Palmowski
    • 1
    • 2
    • 3
  • Jochen Huppert
    • 1
    • 2
  • Eva C. Woenne
    • 1
    • 2
  • Margareta M. Mueller
    • 4
  • Wolfhard Semmler
    • 2
  • Fabian Kiessling
    • 1
    • 2
  1. 1.Junior Group Molecular ImagingGerman Cancer Research CenterHeidelbergGermany
  2. 2.Department of Medical Physics in RadiologyGerman Cancer Research CenterHeidelbergGermany
  3. 3.Department of Diagnostic RadiologyUniversity of HeidelbergHeidelbergGermany
  4. 4.Group Tumor and MicroenvironmentGerman Cancer Research CenterHeidelbergGermany

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