Andrej Lyshchik MD, Presenter: Research suppport, VisualSonics Inc, Toronto, Canada

Debbie Lee, Abstract Co-Author: Nothing to Disclose

Mary Loveless BS, Abstract Co-Author: Nothing to Disclose

Thomas Yankeelov PhD, Abstract Co-Author: Nothing to Disclose

Arthur Carroll Fleischer MD, Abstract Co-Author: Nothing to Disclose

John C. Gore PhD, Abstract Co-Author: Nothing to Disclose

The purpose of this study was to assess relationships between retention of vascular endothelial growth factor receptor type-2 (VEGFR-2) targeted ultrasound contrast agent (UCA) and volume, microvascular cross-sectional area and blood flow velocity in breast cancer tumors.

Six athymic nude mice with implanted 67NR breast cancer tumors were examined with ultrasonography (US) using a VisualSonics Vevo770 scanner with a 40 MHz probe. Tumor volume was evaluated with 3D US. To assess microvascular cross-sectional area and blood flow velocity mice were injected with 50 μL of UCA. The UCA was allowed to reach a pseudo-steady state, after which a high-mechanical index pulse was delivered to destroy UCA. Ultrasonic signal intensity time courses due to UCA replenishment were acquired and analyzed. After a 10 min interval a 50 μL bolus of UCA bearing an anti-VEGFR-2 antibodies was injected. Targeted contrast-enhanced ultrasound images were analyzed by calculation of the normalized video intensity amplitudes caused by backscatter of VEGFR-2 bound UCA. Western blotting and immunohistochemistry on tumor samples were performed to quantify expression of VEGFR-2. Microvascular density was quantified in frozen sections of the tumors perfused with FITC-conjugated tomato lectin.

Retention of VEGFR-2-targeted UCA showed significant negative correlation with tumor size (R2 = 0.81) that may be explained by downregulation of VEGFR-2 expression in large tumors. In addition, retention of VEGFR-2-targeted UCA showed significant positive correlation with values of microvascular cross-sectional area (R2 = 0.58) and negative correlation with blood flow velocity (R2 = 0.67).

Targeted contrast-enhanced high-frequency ultrasonography enables in vivo detection of VEGFR-2. However, retention of VEGFR-2-targeted UCA is influenced by tumor microvascular density and blood flow velocity. Those characteristics should be taken into consideration for accurate quantification of molecular ultrasound signal.

Tumor perfusion affect retention of VEGFR-2-targeted UCA. It should be taken into consideration for accurate quantification of molecular ultrasound signal.

Lyshchik, A, Lee, D, Loveless, M, Yankeelov, T, Fleischer, A, Gore, J, Relationships between Retention of VEGFR-2-targeted Ultrasound Contrast Agent and Volume, Microvascular Cross-Sectional Area, and Blood Flow Velocity in Breast Cancer Tumors.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5011851.html