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The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55)

  • Molecular Imaging
  • Published:
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Abstract

Objectives

Tumour xenografts of well-discernible sizes can be examined well by molecular ultrasound. Here, we investigated whether very early breast carcinomas express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging with targeted microbubbles.

Methods

MCF-7 breast cancer xenografts were orthotopically implanted in nude mice (n = 26). Tumours measuring from 4 mm3 (2 mm diameter) up to 65 mm3 (5 mm diameter) were examined with automated 3D molecular ultrasound using clinically translatable VEGFR2-targeted microbubbles (BR55). Additionally, the relative tumour blood volume was assessed with non-targeted microbubbles (BR38). In vivo ultrasound data were validated by quantitative immunohistochemistry.

Results

Very small lesions 2 mm in diameter showed the highest binding of VEGFR2-specific microbubbles. In larger tumours significantly less BR55 accumulated (p = 0.023). Nonetheless, binding of VEGFR2-targeted microbubbles was still high enough for imaging. The relative blood volume was comparable at all tumour sizes. Both findings were confirmed by immunohistochemistry. Additionally, a significantly enhanced number of large and mature vessels were detected with increasing tumour size (p < 0.01), explaining the decrease in VEGFR2 expression during tumour growth.

Conclusions

3D molecular ultrasound using BR55 is very well suited to depicting the angiogenic activity in very small breast lesions, suggesting its potential for detecting and characterising these lesions.

Key Points

• Xenografts implanted into nude mice offer new insights into breast cancer.

• Small MCF-7 breast xenografts (2 mm) exhibit greater VEGFR2 expression than larger tumours.

• 3D molecular ultrasound with BR55 microbubbles accurately depicts the high angiogenic activity.

• Detecting and characterising small cancers with molecular ultrasound may become possible.

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Authors and Affiliations

  1. Institute for Experimental Molecular Imaging, RWTH-Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany

    Jessica Bzyl, Moritz Palmowski, Anne Rix, Susanne Arns, Josef Ehling, Fabian Kiessling & Wiltrud Lederle

  2. Department of Nuclear Medicine, RWTH-Aachen University, Aachen, Germany

    Moritz Palmowski

  3. Bracco Suisse SA, Geneva, Switzerland

    Jean-Marc Hyvelin & Sibylle Pochon

  4. Institute of Pathology, RWTH-Aachen University, Aachen, Germany

    Josef Ehling

  5. Department of Diagnostic and Interventional Radiology, RWTH-Aachen University, Aachen, Germany

    Simone Schrading

Authors
  1. Jessica Bzyl
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  2. Moritz Palmowski
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  3. Anne Rix
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  4. Susanne Arns
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  5. Jean-Marc Hyvelin
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  6. Sibylle Pochon
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  7. Josef Ehling
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  10. Wiltrud Lederle
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Corresponding author

Correspondence to Fabian Kiessling.

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Bzyl, J., Palmowski, M., Rix, A. et al. The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55). Eur Radiol 23, 468–475 (2013). https://doi.org/10.1007/s00330-012-2594-z

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  • DOI: https://doi.org/10.1007/s00330-012-2594-z

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