Journal of Korean Society of Ultrasound in Medicine 2011;30(2): 147-154.
US Contrast Enhanced Study as an Imaging Biomarker of Anti-cancer Drug Treatment: Preliminary Study with Paclitaxel and a Xenograft Mouse Tumor Model.
Hak Jong Lee, Sung Il Hwang, Jonghoe Byun, Hoon Young Kong, Hyun Sook Jung, Mira Kang
1Department of Radiology, Seoul National University College of Medicine and Seoul National University Bundang Hostpital, Korea.
2Department of Molecular Biology, Dankook University, Korea.
  Published online: June 1, 2011.
PURPOSE: We wanted to assess tumor angiogenesis of human prostate cancer cells (PC3) implanted in mice before and after paclitaxel injection via contrast-enhanced ultrasonography (CEUS). MATERIALS AND METHODS: Twelve mice were injected with human prostate cancer cells (PC3) on the back or hind limbs. The mice were grouped into two groups; one was the paclitaxel treated group (n = 6) and the other was the control group, which was treated with normal saline (n = 6). Before injection of paclitaxel into the peritoneal cavity, baseline CEUS was performed by the administration of 500 microl (1x108 microbubbles) of contrast agent. The area under the curve (AUC) up to 50 seconds after contrast injection was derived from the time-intensity curves. After injection of paclitaxel or saline, one week follow up CEUS studies were performed. The changes of the tumor volume and the AUC in both two groups were evaluated. After CEUS, the mice were sacrificed and the microvessel density (MVD) was compared. RESULTS: In the paclitaxel treated group, the AUC from CEUS showed a significant decrease one week after paclitaxel administration (p = 0.03), even though the tumor volume showed no significant changes (p = 0.116). In the control group, there was no significant decrease of the AUC (p = 0.173). Pathologically, there was a significant difference of microvessel density in both groups (p = 0.002). CONCLUSION: The AUC from the time intensity curve derived from CEUS showed early change in response to the anti-cancer drug treatment in advance of a tumor size response. The findings of CEUS could be an imaging biomarker for assessing the tumor response to anti-cancer drug treatment.
Keywords: Ultrasound; Contrast agent; Angiogenesis; Anti-cancer treatment; Animal study
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