EMAN RESEARCH PUBLISHING | Journal | <p>Microbubbles and electromagnetic waves for the treatment of angiogenesis-dependent human ailments</p>
Angiogenesis biology and therapeutics
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Microbubbles and electromagnetic waves for the treatment of angiogenesis-dependent human ailments

Pegah Moradi

+ Author Affiliations

Journal of Angiotherapy 1(1) 018-021 https://doi.org/10.25163/angiotherapy.11000310419100517

Submitted: 19 February 2017  Revised: 30 April 2017  Published: 10 May 2017 

Targeted ultrasound appears practical for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive evaluation of therapy effects in vivo.  


Molecular imaging such as ultrasound is capable of clarifying the expression of angiogenic markers in vivo. However, the capability of the method for volumetric “multitarget quantification” and for the test of anti-angiogenic therapy response has been investigated partly. Histologic data indicates that high concentrations of VEGFR-2 and of αvβ3 integrin during the growth of tumours are associated with an upregulation of the densities of markers by the endothelial cells, while a down-regulation of during therapy is due to decreasing relative vessel density. Therefore, targeted ultrasound appears practical for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive evaluation of therapy effects in vivo.  

Keywords: Tumour angiogenesis, VEGF ultrasound, Contrast enhanced ultrasound


Alcazar, J.L. (2006). Tumor angiogenesis assessed by three-dimensional power Doppler ultrasound in early, advanced and metastatic ovarian cancer: a preliminary study. Ultrasound in obstetrics & gynecology, 28(3), 325-329.

Bagri, A., et al. (2010). Use of anti-VEGF adjuvant therapy in cancer: challenges and rationale. Trends in molecular medicine, 16(3), 122-132.

Babes, L., et al. (1999). Synthesis of iron oxide nanoparticles used as MRI contrast agents: a parametric study. Journal of colloid and interface science, 212(2), 474-482.

Bloch, S.H., P. Dayton, and K.W. Ferrara. (2004). Targeted imaging using ultrasound contrast agents. Engineering in Medicine and Biology Magazine, IEEE, 23(5), 18-29.

Cai, W. and X. Chen. (2006). Multimodality imaging of vascular endothelial growth factor and vascular endothelial growth factor receptor expression. Frontiers in bioscience: a journal and virtual library, 12, 4267-4279.

Cosgrove, D. (2014). Angiogenesis imaging–ultrasound. The British journal of radiology.

Cheung, A.M., et al. (2007). Detecting vascular changes in tumour xenografts using micro-ultrasound and micro-CT following treatment with VEGFR-2 blocking antibodies. Ultrasound in medicine & biology, 33(8), 1259-1268.

Carmeliet, P. and R.K. Jain,. (2000). Angiogenesis in cancer and other diseases. nature,  407(6801), 249-257.

Chi, A.S., et al. (2009). Angiogenesis as a therapeutic target in malignant gliomas. The oncologist,  14(6), 621-636.

Drevs, J., et al. (2000). Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Research, 60(17), 4819-4824.

Dewitte, H., et al. (2011). The use of ultrasound contrast agents in cancer immunotherapy: The use of mRNA-loaded microbubbles for transfection of dendritic cells. Parallel HOW TO session.

Duda, D.G., et al. (2007). VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects. Trends in molecular medicine, 13(6), 223-230.

Ferrara, N. (2004). Vascular endothelial growth factor: basic science and clinical progress. Endocrine reviews, 25(4), 581-611.

Folkman, J. (1995). Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature medicine, 1(1), 27-30.

Forsberg, F., et al. (2004). Assessment of angiogenesis: implications for ultrasound imaging. Ultrasonics, 42(1), 325-330.

Forsberg, F., et al. (2002). Comparing contrast-enhanced ultrasound to immunohistochemical markers of angiogenesis in a human melanoma xenograft model: preliminary results. Ultrasound in medicine & biology, 28(4), 445-451.

Fujii, H., et al. (2013). Optimization of ultrasound-mediated anti-angiogenic cancer gene therapy. Molecular Therapy—Nucleic Acids, 2(5),  e94.

Grothey, A. and E. Galanis. (2009). Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nature reviews Clinical oncology, 6(9), 507-518.

Hicklin, D.J. and L.M. Ellis. (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of clinical oncology,  23(5), 1011-1027.

Halpern, E.J. and S.E. Strup. (2000). Using gray-scale and color and power Doppler sonography to detect prostatic cancer. American Journal of Roentgenology, 174(3), 623-627.

Hata, K., et al. (1998). Expression of thymidine phosphorylase in malignant ovarian tumors: correlation with microvessel density and an ultrasound-derived index of angiogenesis. Ultrasound in obstetrics & gynecology, 12(3), 201-206.

Kwok, S.J., et al. (2013). Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power doppler ultrasound. Ultrasound in medicine & biology, 39(11), 1983-1990.

Kadambi, A., et al. (2001). Vascular Endothelial Growth Factor (VEGF)-C Differentially Affects Tumor Vascular Function and Leukocyte Recruitment Role of VEGF-Receptor 2 and Host VEGF-A. Cancer research, 61(6), 2404-2408.

Korpanty, G., et al. (2007). Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clinical Cancer Research, 13(1), 323-330.

Kittel, C., P. McEuen, and P. McEuen. (1976). Introduction to solid state physics. Vol. 8, Wiley New York.

Korpanty, G., et al. (2005). Targeting vascular endothelium with avidin microbubbles. Ultrasound in medicine & biology, 31(9), 1279-1283.
Korpanty, G., et al. (2005). Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles. Gene therapy, 12(17), 1305-1312.

Leong-Poi, H. (2009). Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy. Cardiovascular research, 84(2), 190-200.

Liang, H. and M. Blomley. (2014). The role of ultrasound in molecular imaging. The British journal of radiology.

Massoud, T.F. and S.S. Gambhir. (2003). Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes & development, 17(5), 545-580.

Prewett, M., et al. (1999). Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer research, 59(20), 5209-5218.

Selleck, S.B. (2006). Signaling from across the way: transactivation of VEGF receptors by HSPGs. Molecular cell, 22(4), 431-432.
Sun, J., et al. (2005). Inhibiting angiogenesis and tumorigenesis by a synthetic molecule that blocks binding of both VEGF and PDGF to their receptors. Oncogene, 24(29), 4701-4709.

Shohet, R.V., et al. (2000). Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation, 101(22), 2554-2556.

Tsuzuki, Y., et al. (2000). Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1α→ hypoxia response element→ VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer research, 60(22), 6248-6252.

Tortora, G., F. Ciardiello, and G. Gasparini. (2008). Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nature Clinical Practice Oncology, 5(9), 521-530.

Turkbey, B., et al. (2009). Imaging of tumor angiogenesis: functional or targeted? AJR. American journal of roentgenology, 193(2), 304.
Watanabe, H., et al. (2004). Anti-vascular endothelial growth factor receptor-2 (Flk-1/KDR) antibody suppresses contact hypersensitivity. Experimental dermatology, 13(11),  671-681.

Wink, M.H., et al. (2006). Ultrasound imaging and contrast agents: A safe alternative to MRI? Minimally Invasive Therapy & Allied Technologies, 15(2), 93-100.

Willmann, J.r.K., et al. (2008). US Imaging of Tumor Angiogenesis with Microbubbles Targeted to Vascular Endothelial Growth Factor Receptor Type 2 in Mice 1. Radiology, 246(2), 508-518.

Yang, W.T., et al. (2002). Correlation between color power Doppler sonographic measurement of breast tumor vasculature and immunohistochemical analysis of microvessel density for the quantitation of angiogenesis. Journal of ultrasound in medicine, 21(11), 1227-1235.

Young, S. and M. Dyson. (1990). The effect of therapeutic ultrasound on angiogenesis. Ultrasound in medicine & biology, 16(3), 261-269.

Zhu, A.X., et al. (2011). HCC and angiogenesis: possible targets and future directions. Nature reviews Clinical oncology, 8(5), 292-301.

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