European Radiology

, Volume 21, Issue 9, pp 1988–1995 | Cite as

Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38)

  • Jessica Bzyl
  • Wiltrud Lederle
  • Anne Rix
  • Christoph Grouls
  • Isabelle Tardy
  • Sibylle Pochon
  • Monica Siepmann
  • Tobias Penzkofer
  • Michel Schneider
  • Fabian Kiessling
  • Moritz Palmowski
Molecular Imaging



To characterise clinically translatable long-circulating (BR38) and VEGFR2-targeted (BR55) microbubbles (MB) and to assess their ability to discriminate breast cancer models with different aggressiveness.


The circulation characteristics of BR38 and BR55 were investigated in healthy mice. The relative blood volume (rBV) of MDA-MB-231 (n = 5) or MCF-7 (n = 6) tumours was determined using BR38. In the same tumours in-vivo binding specificity of BR55 was tested and VEGFR2 expression assessed. Data validation included quantitative immunohistological analysis.


BR38 had a longer blood half-life than BR55 (>600 s vs. 218 s). BR38-enhanced ultrasound showed greater vascularisation in MDA-MB-231 tumours (p = 0.022), which was in line with immunohistology (p = 0.033). In-vivo competitive binding experiments proved the specificity of BR55 to VEGFR2 (p = 0.027). Binding of BR55 was significantly higher in MDA-MB-231 than in MCF-7 tumours (p = 0.049), which corresponded with the VEGFR2 levels found histologically (p = 0.015). However, differences became smaller when normalising the levels of BR55 to the rBV.


BR38 and BR55 are well suited to characterising and distinguishing breast cancers with different angiogenesis and aggressiveness. Long-circulating BR38 MB allow extensive 3-dimensional examinations of larger or several organs. BR55 accumulation faithfully reflects the VEGFR2 status in tumours and depicts even small differences in angiogenesis.


Functional and molecular ultrasound Angiogenesis VEGFR2 Breast cancer 


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Copyright information

© European Society of Radiology 2011

Authors and Affiliations

  • Jessica Bzyl
    • 1
  • Wiltrud Lederle
    • 1
  • Anne Rix
    • 1
  • Christoph Grouls
    • 1
    • 2
  • Isabelle Tardy
    • 3
  • Sibylle Pochon
    • 3
  • Monica Siepmann
    • 4
  • Tobias Penzkofer
    • 2
  • Michel Schneider
    • 3
  • Fabian Kiessling
    • 1
  • Moritz Palmowski
    • 1
    • 2
    • 5
  1. 1.Institute for Experimental Molecular ImagingRWTH-Aachen UniversityAachenGermany
  2. 2.Department of RadiologyRWTH-Aachen UniversityAachenGermany
  3. 3.Bracco Research SAGenevaSwitzerland
  4. 4.Institute of Medical EngineeringRuhr-University BochumBochumGermany
  5. 5.Department of Nuclear MedicineRWTH-Aachen UniversityAachenGermany

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