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Dose-response relationship of ultrasound contrast agent in an in vivo murine melanoma model

Abstract

Many factors affect the sensitivity and reliability of tumor vasculature assessment at the small doses of contrast agent necessary for imaging mice. In this study we investigate the dose-response relationship of ultrasound contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of contrast agents, Optison and Definity. Six mice were treated with an antivascular agent, combretastatin A4-phosphate (CA4P), and imaged before and after treatment. The color-weighted fractional area (CWFA) of the peak-enhanced image was measured to assess tumor perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with dose (R2 = 0.97). Treatment with CA4P resulted in pronounced reduction in tumor perfusion 2 h after contrast injection, but perfusion recovered in the tumor periphery after 2 days. CWFA was significantly different between pre- and posttreatment for all doses at 2 h and 2 days (p < 0.05, respectively). There was no significant difference detectable between the two contrast agents, Optison and Definity (p = 0.46). In vivo tumor enhancement in mice increases as logarithmic function with dose. Although the extent of enhancement is dose dependent, the difference between pre- and post-therapy enhancement is relatively unchanged and uniform at varying doses. The two contrast agents tested in this study performed equally well. These results suggest that quantitative contrast-enhanced power Doppler imaging is an effective method for monitoring therapy response of tumors in mice.

Author

Gabriela S Seiler, Lisa S Ziemer, Susan Schultz, William M.F Lee and Chandra M Sehgal

Contact Details

Corresponding address:
Gabriela Seiler, Assistant Professor of Radiology, Matthew J. Ryan Veterinary Hospital,
University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA, 19104-6010, USA

Reference

ICIS Cancer Imaging Volume 7 Issue 1
DOI: 10.1102/1470-7330.2007.0031

Date Posted

17 December 2007

Open Access is provided for this article.

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