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© 2005 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 24:349-354 • 0278-4297

Contrast-Aided Diagnostic Ultrasound Does Not Enhance Lung Metastasis in a Mouse Melanoma Tumor Model

Douglas L. Miller, PhD and Chunyan Dou, MD

Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan USA.

Address correspondence and reprint requests to Douglas L. Miller, PhD, University of Michigan Medical Center, Room 3315, Kresge III, 200 Zina Pitcher Pl, Ann Arbor, MI 48109-0553 USA. E-mail: douglm{at}umich.edu

Objective. The purpose of this research was to test the hypothesis that contrast-aided diagnostic ultrasound (CADUS) could exacerbate the metastatic spread of mouse melanoma tumor cells to the lungs. Methods. The melanoma cell lines B16 and B16-D5 (metastatic specifically to lung) were implanted on a hind leg of female C57/bl6 mice. Growing tumors were scanned by 1.5-MHz diagnostic ultrasound in a 37°C water bath. Four hundred image frames were triggered at a 1-Hz rate with 4 retro-orbital injections of an ultrasonographic contrast agent at dosage of 10 µL/kg at 100-second intervals. Sham-treated mice received 400 frames of ultrasonography followed by the contrast agent with the ultrasound off. The primary tumor was surgically removed 1 day after ultrasound administration. Lungs were removed and evaluated blind after 2 weeks of bleaching in Fekete solution. Results. Three experiments were performed. The first experiment involved scanning sham and CADUS groups of 20 mice each with B16 tumors; B16 metastasis was not enhanced. The second experiment repeated this test with the D5 cell line; the metastasis enhancement was marginally significant for average number (0.3 and 3.2; P = .06) and incidence (3 and 9 of 19; P = .08) in mice without tumor recurrence. Finally, a third experiment was performed to clarify ambiguous results in the second experiment and consisted of 2 groups of 40 mice each. In this larger experiment, the results were essentially equal for the sham and CADUS groups. Conclusions. Overall, the results do not support the hypothesis of CADUS-enhanced metastasis.

Key Words: adverse effects • cancer • contrast agent • diagnostic ultrasound • metastasis

Abbreviations: CADUS, contrast-aided diagnostic ultrasound • PRPA, peak rarefactional pressure amplitude




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