Monitoring angiogenesis in human melanoma xenograft model using contrast-enhanced ultrasound imaging.
The potential for noninvasive monitoring and quantification of tumor angiogenesis with contrast-enhanced ultrasound imaging has been investigated in a murine cancer model. Seventy athymic nude mice were implanted with the human melanoma cell line DB-1 but only 30 of these were available for the final study. The 30 mice were divided into three groups (10 mice/group), which were studied with contrast-enhanced ultrasound imaging 4, 5 or 6 weeks post-implantation. Power Doppler and pulse inversion harmonic imaging (PIHI) were performed (in real time and intermittently) with a Sonoline Elegra scanner (Siemens Medical Solutions, Issaquah, WA) following injection of Optison (dose: 0.4-0.6 ml/kg; GE Healthcare, Princeton, NJ). Ultrasound results were compared to immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). Linear regression analysis indicated statistically significant correlations between the percent area stained with VEGF and ultrasound measures of tumor neovascularity obtained with all three techniques (p < 0.01). Contrast-enhanced ultrasound imaging of tumor neovascularity appears to provide a noninvasive marker of angiogenesis corresponding to the expression of VEGF in the DB-1 model and may become a useful tool for monitoring clinical anti-angiogenic therapies.
Forsberg
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F
Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA. flemming.forsberg@jefferson.edu
Ro
R J
RJ
Liu
J B
JB
Lipcan
K J
KJ
Potoczek
M
M
Nazarian
L N
LN
D000418:Albumins; D000704:Analysis of Variance; D000818:Animals; D014408:Biomarkers, Tumor; D003287:Contrast Media; D051546:Cyclooxygenase 2 / Q000032:analysis; D004195:Disease Models, Animal; D042783:Endothelial Cells; D005260:Female; D005466:Fluorocarbons; D007089:Image Enhancement / Q000379:methods*; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D008991:Monitoring, Physiologic / Q000379:methods; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging*; D014407:Tumor Cells, Cultured; D018608:Ultrasonography, Doppler / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
D000418:Albumins; D014408:Biomarkers, Tumor; D003287:Contrast Media; C099458:FS 069; D005466:Fluorocarbons; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2