Skip to main content
SpringerLink
Log in

Contrast Ultrasound in Imaging Tumor Angiogenesis

  • Chapter
  • First Online:
Vascular Disruptive Agents for the Treatment of Cancer

  • 341 Accesses

Abstract

New strategies to detect tumor angiogenesis and monitor response of tumor vasculature to therapy are needed. There are a plethora of anti-angiogenic strategies being evaluated pre-clinically and in the clinical setting; however, a ­significant unmet challenge is following the response of tumors to anti-angiogenic therapy. Herein we review current modalities being investigated for this purpose and highlight the utility of contrast ultrasound imaging using targeted microbubbles (MB). MB are small (1–10 μm) gas-filled intravascular tracers. MB can be targeted via antibodies, peptides or other moieties to virtually any endothelial cell surface marker and thus selectively mark specific vascular beds (e.g., tumor blood vessels). Furthermore targeted MB can be used to non-invasively evaluate the expression level of particular molecular antigens (e.g., CD105, VEGFR2) and monitor the effect of therapy on target expression. We conclude that targeted MB represent a novel and attractive tool for non-invasive, vascular-targeted molecular imaging of tumor angiogenesis and for monitoring vascular effects specific to anti-tumor therapy in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

APN:

aminopeptidase N

BV:

blood vessels

EC:

endothelial cells

FN:

fibronectin

MMP:

matrix metalloproteinases

PSMA:

prostate specific membrane antigen

SMC:

smooth muscle cell

TEM:

tumor endothelial marker

VEGF:VEGFR:

complex of VEGF and its receptor

References

  • Asano, M., Yukita, A., and Suzuki, H. (1999). Wide spectrum of antitumor activity of a ­neutralizing monoclonal antibody to human vascular endothelial growth factor. Jpn J Cancer Res 90, 93–100.

    PubMed  CAS  Google Scholar 

  • Baluk, P., Hashizume, H., and McDonald, D. M. (2005). Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15, 102–111.

    PubMed  CAS  Google Scholar 

  • Barrett, T., Brechbiel, M., Bernardo, M., and Choyke, P. L. (2007). MRI of tumor angiogenesis. J Magn Reson Imaging 26, 235–249.

    PubMed  Google Scholar 

  • Borsi, L., Balza, E., Bestagno, M., Castellani, P., Carnemolla, B., Biro, A., Leprini, A., Sepulveda, J., Burrone, O., Neri, D., and Zardi, L. (2002). Selective targeting of tumoral vasculature: comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin. Int J Cancer 102, 75–85.

    PubMed  CAS  Google Scholar 

  • Brekken, R. A., Huang, X., King, S. W., and Thorpe, P. E. (1998). Vascular endothelial growth factor as a marker of tumor endothelium. Cancer Res 58, 1952–1959.

    PubMed  CAS  Google Scholar 

  • Brekken, R. A., Overholser, J. P., Stastny, V. A., Waltenberger, J., Minna, J. D., and Thorpe, P. E. (2000). Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. Cancer Res 60, 5117–5124.

    PubMed  CAS  Google Scholar 

  • Brooks, P. C., Clark, R. A., and Cheresh, D. A. (1994). Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264, 569–571.

    PubMed  CAS  Google Scholar 

  • Broumas, A. R., Pollard, R. E., Bloch, S. H., Wisner, E. R., Griffey, S., and Ferrara, K. W. (2005). Contrast-enhanced computed tomography and ultrasound for the evaluation of tumor blood flow. Invest Radiol 40, 134–147.

    PubMed  Google Scholar 

  • Burg, M. A., Pasqualini, R., Arap, W., Ruoslahti, E., and Stallcup, W. B. (1999). NG2 proteoglycan-binding peptides target tumor neovasculature. Cancer Res 59, 2869–2874.

    PubMed  CAS  Google Scholar 

  • Burrows, F. J., Derbyshire, E. J., Tazzari, P. L., Amlot, P., Gazdar, A. F., King, S. W., Letarte, M., Vitetta, E. S., and Thorpe, P. E. (1995). Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. Clin Cancer Res 1, 1623–1634.

    PubMed  CAS  Google Scholar 

  • Carnemolla, B., Neri, D., Castellani, P., Leprini, A., Neri, G., Pini, A., Winter, G., and Zardi, L. (1996). Phage antibodies with pan-species recognition of the oncofoetal angiogenesis marker fibronectin ED-B domain. Int J Cancer 68, 397–405.

    PubMed  CAS  Google Scholar 

  • Castell, F., and Cook, G. J. (2008). Quantitative techniques in 18FDG PET scanning in oncology. Br J Cancer 98, 1597–1601.

    PubMed  CAS  Google Scholar 

  • Cheng, S. C., Dy, T. C., and Feinstein, S. B. (1998). Contrast echocardiography: review and future directions. Am J Cardiol 81, 41G-48G.

    PubMed  CAS  Google Scholar 

  • Cherrington, J. M., Strawn, L. M., and Shawver, L. K. (2000). New paradigms for the treatment of cancer: the role of anti-angiogenesis agents. Adv Cancer Res 79, 1–38.

    PubMed  CAS  Google Scholar 

  • Cohen, J. L., Cheirif, J., Segar, D. S., Gillam, L. D., Gottdiener, J. S., Hausnerova, E., and Bruns, D. E. (1998). Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III multicenter trial. J Am Coll Cardiol 32, 746–752.

    PubMed  CAS  Google Scholar 

  • Cooke, S. P., Boxer, G. M., Lawrence, L., Pedley, R. B., Spencer, D. I., Begent, R. H., and Chester, K. A. (2001). A strategy for antitumor vascular therapy by targeting the vascular endothelial growth factor: receptor complex. Cancer Res 61, 3653–3659.

    PubMed  CAS  Google Scholar 

  • Correas, J. M., Bridal, L., Lesavre, A., Mejean, A., Claudon, M., and Helenon, O. (2001). Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts. Eur Radiol 11, 1316–1328.

    PubMed  CAS  Google Scholar 

  • Cwajg, J., Xie, F., O’Leary, E., Kricsfeld, D., Dittrich, H., and Porter, T. R. (2000). Detection of angiographically significant coronary artery disease with accelerated intermittent imaging after intravenous administration of ultrasound contrast material. Am Heart J 139, 675–683.

    PubMed  CAS  Google Scholar 

  • Dayton, P. A., and Ferrara, K. W. (2002). Targeted imaging using ultrasound. J Magn Reson Imaging 16, 362–377.

    PubMed  Google Scholar 

  • de Langen, A. J., van den Boogaart, V. E., Marcus, J. T., and Lubberink, M. (2008). Use of H2(15)O-PET and DCE-MRI to measure tumor blood flow. Oncologist 13, 631–644.

    PubMed  Google Scholar 

  • Duda, D. G., Jain, R. K., and Willett, C. G. (2007). Antiangiogenics: the potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol 25, 4033–4042.

    PubMed  CAS  Google Scholar 

  • Dugdale, P. E., Miles, K. A., Bunce, I., Kelley, B. B., and Leggett, D. A. (1999). CT measurement of perfusion and permeability within lymphoma masses and its ability to assess grade, activity, and chemotherapeutic response. J Comput Assist Tomogr 23, 540–547.

    PubMed  CAS  Google Scholar 

  • Eberhard, A., Kahlert, S., Goede, V., Hemmerlein, B., Plate, K. H., and Augustin, H. G. (2000). Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 60, 1388–1393.

    PubMed  CAS  Google Scholar 

  • Ellegala, D. B., Leong-Poi, H., Carpenter, J. E., Klibanov, A. L., Kaul, S., Shaffrey, M. E., Sklenar, J., and Lindner, J. R. (2003). Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. Circulation 108, 336–341.

    PubMed  Google Scholar 

  • Epstein, A. L., Khawli, L. A., Hornick, J. L., and Taylor, C. R. (1995). Identification of a monoclonal antibody, TV-1 directed against the basement membrane of tumor vessels, and its use to enhance the delivery of macromolecules to tumors after conjugation with interleukin 2. Cancer Res 55, 2673–2680.

    PubMed  CAS  Google Scholar 

  • Ferrara, N. (2002). VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2, 795–803.

    PubMed  CAS  Google Scholar 

  • Ferrara, N., and Kerbel, R. S. (2005). Angiogenesis as a therapeutic target. Nature 438, 967–974.

    PubMed  CAS  Google Scholar 

  • Ferrara, N., Gerber, H. P., and LeCouter, J. (2003). The biology of VEGF and its receptors. Nat Med 9, 669–676.

    PubMed  CAS  Google Scholar 

  • Ferrara, N., Hillan, K. J., and Novotny, W. (2005). Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333, 328–335.

    PubMed  CAS  Google Scholar 

  • Folkman, J. (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med 285, 1182–1186.

    PubMed  CAS  Google Scholar 

  • Folkman, J. (1995). Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1, 27–31.

    PubMed  CAS  Google Scholar 

  • Forsberg, F., Goldberg, B. B., Liu, J. B., Merton, D. A., Rawool, N. M., and Shi, W. T. (1999). Tissue-specific US contrast agent for evaluation of hepatic and splenic parenchyma. Radiology 210, 125–132.

    PubMed  CAS  Google Scholar 

  • Franklin, D. L., Schlegel, W., and Rushmer, R. F. (1961). Blood flow measured by Doppler frequency shift of back-scattered ultrasound. Science 134, 564–565.

    PubMed  CAS  Google Scholar 

  • Fry, W. J., Mosberg, W. H., Jr., Barnard, J. W., and Fry, F. J. (1954). Production of focal destructive lesions in the central nervous system with ultrasound. J Neurosurg 11, 471–478.

    PubMed  CAS  Google Scholar 

  • Gasparini, G., Brooks, P. C., Biganzoli, E., Vermeulen, P. B., Bonoldi, E., Dirix, L. Y., Ranieri, G., Miceli, R., and Cheresh, D. A. (1998). Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin Cancer Res 4, 2625–2634.

    PubMed  CAS  Google Scholar 

  • Gerber, H.-P., Kowalski, J, Sherman, D, et al. (2000). Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Research 60, 6253–6258.

    PubMed  CAS  Google Scholar 

  • Gonzalez, A. M., Gonzales, M., Herron, G. S., Nagavarapu, U., Hopkinson, S. B., Tsuruta, D., and Jones, J. C. (2002). Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo. Proc Natl Acad Sci U S A 99, 16075–16080.

    PubMed  CAS  Google Scholar 

  • Gossmann, A., Helbich, T. H., Kuriyama, N., Ostrowitzki, S., Roberts, T. P., Shames, D. M., van Bruggen, N., Wendland, M. F., Israel, M. A., and Brasch, R. C. (2002). Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiforme. J Magn Reson Imaging 15, 233–240.

    PubMed  Google Scholar 

  • Gramiak, R., and Shah, P. M. (1968). Echocardiography of the aortic root. Invest Radiol 3, 356–366.

    PubMed  CAS  Google Scholar 

  • Greenberg, J. I., Shields, D. J., Barillas, S. G., Acevedo, L. M., Murphy, E., Huang, J., Scheppke, L., Stockmann, C., Johnson, R. S., Angle, N., and Cheresh, D. A. (2008). A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 456, 809–813.

    PubMed  CAS  Google Scholar 

  • Griffioen, A. W., Coenen, M. J., Damen, C. A., Hellwig, S. M., van Weering, D. H., Vooys, W., Blijham, G. H., and Groenewegen, G. (1997). CD44 is involved in tumor angiogenesis; an activation antigen on human endothelial cells. Blood 90, 1150–1159.

    PubMed  CAS  Google Scholar 

  • Hagemeier, H.-H., Vollmer, E., Goerdt, S., Schulze-Osthoff, K., and Sorg, C. (1986). A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non-reactive with normal adult tissues. Int J Cancer 38, 481–488.

    PubMed  CAS  Google Scholar 

  • Harvey, C. J., Blomley, M. J., Eckersley, R. J., Heckemann, R. A., Butler-Barnes, J., and Cosgrove, D. O. (2000). Pulse-inversion mode imaging of liver specific microbubbles: improved detection of subcentimetre metastases. Lancet 355, 807–808.

    PubMed  CAS  Google Scholar 

  • Ismail, S., Jayaweera, A. R., Camarano, G., Gimple, L. W., Powers, E. R., and Kaul, S. (1996). Relation between air-filled albumin microbubble and red blood cell rheology in the human myocardium. Influence of echocardiographic systems and chest wall attenuation. Circulation 94, 445–451.

    PubMed  CAS  Google Scholar 

  • Jaffe, C. C. (2006). Measures of response: RECIST, WHO, and new alternatives. J Clin Oncol 24, 3245–3251.

    PubMed  Google Scholar 

  • Jain, R. K. (2001). Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7, 987–989.

    PubMed  CAS  Google Scholar 

  • Jain, R. K. (2005). Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307, 58–62.

    PubMed  CAS  Google Scholar 

  • Jubb, A. M., Oates, A. J., Holden, S., and Koeppen, H. (2006). Predicting benefit from anti-angiogenic agents in malignancy. Nat Rev Cancer 6, 626–635.

    PubMed  CAS  Google Scholar 

  • Ke, L., Qu, H., Nagy, J. A., Eckelhoefer, I. A., Masse, E. M., Dvorak, A. M., and Dvorak, H. F. (1996). Vascular targeting of solid and ascites tumours with antibodies to vascular endothelial growth factor. Eur J Cancer 32A, 2467–2473.

    Google Scholar 

  • Kim, S., Bell, K., Mousa, S. A., and Varner, J. A. (2000a). Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. Am J Pathol 156, 1345–1362.

    PubMed  CAS  Google Scholar 

  • Kim, T. K., Choi, B. I., Han, J. K., Hong, H. S., Park, S. H., and Moon, S. G. (2000b). Hepatic tumors: contrast agent-enhancement patterns with pulse-inversion harmonic US. Radiology 216, 411–417.

    PubMed  CAS  Google Scholar 

  • Kim, D. W., Huamani, J., Niermann, K. J., Lee, H., Geng, L., Leavitt, L. L., Baheza, R. A., Jones, C. C., Tumkur, S., Yankeelov, T. E., et al. (2006). Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: implications for improvement of therapy schedules. J Ultrasound Med 25, 1507–1517.

    PubMed  Google Scholar 

  • Koch, A. E., Nickoloff, B. J., Holgersson, J., Seed, B., Haines, G. K., Burrows, J. C., and Leibovich, S. J. (1994). 4A11, a monoclonal antibody recognizing a novel antigen expressed on aberrant vascular endothelium. Upregulation in an in vivo model of contact dermatitis. Am J Pathol 144, 244–259.

    PubMed  CAS  Google Scholar 

  • Korpanty, G., Grayburn, P. A., Shohet, R. V., and Brekken, R. A. (2005). Targeting vascular endothelium with avidin microbubbles. Ultrasound Med Biol 31, 1279–1283.

    PubMed  Google Scholar 

  • Korpanty, G., Carbon, J. G., Grayburn, P. A., Fleming, J. B., and Brekken, R. A. (2007). Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin Cancer Res 13, 323–330.

    PubMed  CAS  Google Scholar 

  • Krix, M. (2005). Quantification of enhancement in contrast ultrasound: a tool for monitoring of therapies in liver metastases. Eur Radiol 15 Suppl 5, E104–108.

    PubMed  Google Scholar 

  • Krix, M., Plathow, C., Essig, M., Herfarth, K., Debus, J., Kauczor, H. U., and Delorme, S. (2005). Monitoring of liver metastases after stereotactic radiotherapy using low-MI contrast-enhanced ultrasound – initial results. Eur Radiol 15, 677–684.

    PubMed  CAS  Google Scholar 

  • Lanza, G. M., and Wickline, S. A. (2001). Targeted ultrasonic contrast agents for molecular imaging and therapy. Prog Cardiovasc Dis 44, 13–31.

    PubMed  CAS  Google Scholar 

  • Leach, M. O., Brindle, K. M., Evelhoch, J. L., Griffiths, J. R., Horsman, M. R., Jackson, A., Jayson, G., Judson, I. R., Knopp, M. V., Maxwell, R. J., et al. (2003). Assessment of antiangiogenic and antivascular therapeutics using MRI: recommendations for appropriate methodology for clinical trials. Br J Radiol 76 Spec No 1, S87–91.

    Google Scholar 

  • Lee, D. J., Lyshchik, A., Huamani, J., Hallahan, D. E., and Fleischer, A. C. (2008). Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model. J Ultrasound Med 27, 855–866.

    PubMed  Google Scholar 

  • Lindner, J. R., Coggins, M. P., Kaul, S., Klibanov, A. L., Brandenburger, G. H., and Ley, K. (2000a). Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes. Circulation 101, 668–675.

    PubMed  CAS  Google Scholar 

  • Lindner, J. R., Dayton, P. A., Coggins, M. P., Ley, K., Song, J., Ferrara, K., and Kaul, S. (2000b). Noninvasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles. Circulation 102, 531–538.

    PubMed  CAS  Google Scholar 

  • Lindner, J. R., Song, J., Christiansen, J., Klibanov, A. L., Xu, F., and Ley, K. (2001). Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation 104, 2107–2112.

    PubMed  CAS  Google Scholar 

  • Liu, N., Lapcevich, R. K., Underhill, C. B., Han, Z., Gao, F., Swartz, G., Plum, S. M., Zhang, L., and Green, S. J. (2001). Metastatin: a hyaluronan-binding complex from cartilage that inhibits tumor growth. Cancer Res 61, 1022–1028.

    PubMed  CAS  Google Scholar 

  • Lodge, M. A., Carson, R. E., Carrasquillo, J. A., Whatley, M., Libutti, S. K., and Bacharach, S. L. (2000). Parametric images of blood flow in oncology PET studies using [15O]water. J Nucl Med 41, 1784–1792.

    PubMed  CAS  Google Scholar 

  • Lyshchik, A., Fleischer, A. C., Huamani, J., Hallahan, D. E., Brissova, M., and Gore, J. C. (2007). Molecular imaging of vascular endothelial growth factor receptor 2 expression using targeted contrast-enhanced high-frequency ultrasonography. J Ultrasound Med 26, 1575–1586.

    PubMed  Google Scholar 

  • Marty, C., Odermatt, B., Schott, H., Neri, D., Ballmer-Hofer, K., Klemenz, R., and Schwendener, R. A. (2002). Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes. Br J Cancer 87, 106–112.

    PubMed  CAS  Google Scholar 

  • McDonald, D. M., and Choyke, P. L. (2003). Imaging of angiogenesis: from microscope to clinic. Nat Med 9, 713–725.

    PubMed  CAS  Google Scholar 

  • Miller, J. C., Pien, H. H., Sahani, D., Sorensen, A. G., and Thrall, J. H. (2005). Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst 97, 172–187.

    PubMed  CAS  Google Scholar 

  • Molema, G., Meijer, D. K., and de Leij, L. F. (1998). Tumor vasculature targeted therapies: getting the players organized. Biochem Pharmacol 55, 1939–1945.

    PubMed  CAS  Google Scholar 

  • Morgan, K. E., Allen, J. S., Dayton, P. A., Chomas, J. E., Klibaov, A. L., and Ferrara, K. W. (2000). Experimental and theoretical evaluation of microbubble behavior: effect of transmitted phase and bubble size. IEEE Trans Ultrason Ferroelectr Freq Control 47, 1494–1509.

    PubMed  CAS  Google Scholar 

  • Morgan, B., Thomas, A. L., Drevs, J., Hennig, J., Buchert, M., Jivan, A., Horsfield, M. A., Mross, K., Ball, H. A., Lee, L., et al. (2003). Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J Clin Oncol 21, 3955–3964.

    PubMed  CAS  Google Scholar 

  • Niermann, K. J., Fleischer, A. C., Huamani, J., Yankeelov, T. E., Kim, D. W., Wilson, W. D., and Hallahan, D. E. (2007). Measuring tumor perfusion in control and treated murine tumors: co­rrelation of microbubble contrast-enhanced sonography to dynamic contrast-enhanced m­agnetic resonance imaging and fluorodeoxyglucose positron emission tomography. J Ultrasound Med 26, 749–756.

    PubMed  Google Scholar 

  • Nilsson, F., Kosmehl, H., Zardi, L., and Neri, D. (2001). Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. Cancer Res 61, 711–716.

    PubMed  CAS  Google Scholar 

  • Padhani, A. R., and Leach, M. O. (2005). Antivascular cancer treatments: functional assessments by dynamic contrast-enhanced magnetic resonance imaging. Abdom Imaging 30, 324–341.

    PubMed  CAS  Google Scholar 

  • Palmowski, M., Huppert, J., Ladewig, G., Hauff, P., Reinhardt, M., Mueller, M. M., Woenne, E. C., Jenne, J. W., Maurer, M., Kauffmann, G. W., et al. (2008). Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects. Mol Cancer Ther 7, 101–109.

    PubMed  CAS  Google Scholar 

  • Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1997). Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol 15, 542–546.

    PubMed  CAS  Google Scholar 

  • Pasqualini, R., Koivunen, E., Kain, R., Lahdenranta, J., Sakamoto, M., Stryhn, A., Ashmun, R. A., Shapiro, L. H., Arap, W., and Ruoslahti, E. (2000). Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res 60, 722–727.

    PubMed  CAS  Google Scholar 

  • Pollard, R. E., Garcia, T. C., Stieger, S. M., Ferrara, K. W., Sadlowski, A. R., and Wisner, E. R. (2004). Quantitative evaluation of perfusion and permeability of peripheral tumors using contrast-enhanced computed tomography. Invest Radiol 39, 340–349.

    PubMed  Google Scholar 

  • Provenzale, J. M. (2007). Imaging of angiogenesis: clinical techniques and novel imaging methods. AJR Am J Roentgenol 188, 11–23.

    PubMed  Google Scholar 

  • Ran, S., and Thorpe, P. E. (2002). Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy. Int J Radiat Oncol Biol Phys 54, 1479–1484.

    PubMed  CAS  Google Scholar 

  • Ran, S., He, J., Huang, X., Soares, M., Scothorn, D., and Thorpe, P. E. (2005). Antitumor effects of a monoclonal antibody that binds anionic phospholipids on the surface of tumor blood vessels in mice. Clin Cancer Res 11, 1551–1562.

    PubMed  CAS  Google Scholar 

  • Rettig, W. J., Garinchesa, P., Healey, J. H., Su, S. L., Jaffe, E. A., and Old, L. J. (1992). Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. Proc Natl Acad Sci U S A 89, 10832–10836.

    PubMed  CAS  Google Scholar 

  • Rosen, M. A., and Schnall, M. D. (2007). Dynamic contrast-enhanced magnetic resonance imaging for assessing tumor vascularity and vascular effects of targeted therapies in renal cell carcinoma. Clin Cancer Res 13, 770s-776s.

    PubMed  CAS  Google Scholar 

  • Salnikov, A. V., Heldin, N. E., Stuhr, L. B., Wiig, H., Gerber, H., Reed, R. K., and Rubin, K. (2006). Inhibition of carcinoma cell-derived VEGF reduces inflammatory characteristics in xenograft carcinoma. Int J Cancer 119, 2795–2802.

    PubMed  CAS  Google Scholar 

  • Senger, D. R., Claffey, K. P., Benes, J. E., Perruzzi, C. A., Sergiou, A. P., and Detmar, M. (1997). Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Proc Natl Acad Sci U S A 94, 13612–13617.

    PubMed  CAS  Google Scholar 

  • Senger, D. R., Perruzzi, C. A., Streit, M., Koteliansky, V. E., de Fougerolles, A. R., and Detmar, M. (2002). The alpha(1)beta(1) and alpha(2)beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am J Pathol 160, 195–204.

    PubMed  CAS  Google Scholar 

  • Seon, B. K., Matsuno, F., Haruta, Y., Kondo, M., and Barcos, M. (1997). Long-lasting complete inhibition of human solid tumors in SCID mice by targeting endothelial cells of tumor vasculature with antihuman endoglin immunotoxin. Clin Cancer Res 3, 1031–1044.

    PubMed  CAS  Google Scholar 

  • Sessa, C., Guibal, A., Del Conte, G., and Ruegg, C. (2008). Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat Clin Pract Oncol 5, 378–391.

    PubMed  CAS  Google Scholar 

  • Shaked, Y., Bertolini, F., Man, S., Rogers, M. S., Cervi, D., Foutz, T., Rawn, K., Voskas, D., Dumont, D. J., Ben-David, Y., et al. (2005). Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 7, 101–111.

    PubMed  CAS  Google Scholar 

  • Sipkins, D. A., Cheresh, D. A., Kazemi, M. R., Nevin, L. M., Bednarski, M. D., and Li, K. C. (1998). Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med 4, 623–626.

    PubMed  CAS  Google Scholar 

  • Soares, M. M., King, S. W., and Thorpe, P. E. (2008). Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. Nat Med 14, 1357–1362.

    PubMed  CAS  Google Scholar 

  • St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., and Kinzler, K. W. (2000). Genes expressed in human tumor endothelium. Science 289, 1197–1202.

    PubMed  CAS  Google Scholar 

  • Thorpe, P. E., and Burrows, F. J. (1995). Antibody-directed targeting of the vasculature of solid tumors. Breast Cancer ResTreat 36, 237–251.

    Google Scholar 

  • Tofts, P. S., Brix, G., Buckley, D. L., Evelhoch, J. L., Henderson, E., Knopp, M. V., Larsson, H. B., Lee, T. Y., Mayr, N. A., Parker, G. J., et al. (1999). Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10, 223–232.

    PubMed  CAS  Google Scholar 

  • Tomillero, A., and Moral, M. A. (2008). Gateways to clinical trials. Methods Find Exp Clin Pharmacol 30, 643–672.

    PubMed  CAS  Google Scholar 

  • Tong, R. T., Boucher, Y., Kozin, S. V., Winkler, F., Hicklin, D. J., and Jain, R. K. (2004). Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res 64, 3731–3736.

    PubMed  CAS  Google Scholar 

  • Tsushima, Y., Funabasama, S., Aoki, J., Sanada, S., and Endo, K. (2004). Quantitative perfusion map of malignant liver tumors, created from dynamic computed tomography data. Acad Radiol 11, 215–223.

    PubMed  Google Scholar 

  • Villanueva, F. S., and Wagner, W. R. (2008). Ultrasound molecular imaging of cardiovascular disease. Nat Clin Pract Cardiovasc Med 5 Suppl 2, S26–32.

    PubMed  CAS  Google Scholar 

  • Villanueva, F. S., Jankowski, R. J., Manaugh, C., and Wagner, W. R. (1997). Albumin microbubble adherence to human coronary endothelium: implications for assessment of endothelial function using myocardial contrast echocardiography. J Am Coll Cardiol 30, 689–693.

    PubMed  CAS  Google Scholar 

  • Villanueva, F. S., Jankowski, R. J., Klibanov, S., Pina, M. L., Alber, S. M., Watkins, S. C., Brandenburger, G. H., and Wagner, W. R. (1998). Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells. Circulation 98, 1–5.

    PubMed  CAS  Google Scholar 

  • Wang, J. M., Kumar, S., Pye, D., Vanagthoven, A. J., Krupinski, J., and Hunter, R. D. (1993). A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues. Int J Cancer 54, 363–370.

    PubMed  CAS  Google Scholar 

  • Wang, J. M., Kumar, S., van Agthoven, A., Kumar, P., Pye, D., and Hunter, R. D. (1995). Irradiation induces up-regulation of E9 protein (CD105) in human vascular endothelial cells. Int J Cancer 62, 791–796.

    PubMed  CAS  Google Scholar 

  • Weller, G. E., Villanueva, F. S., Tom, E. M., and Wagner, W. R. (2005). Targeted ultrasound contrast agents: in vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewisx. Biotechnol Bioeng 92, 780–788.

    PubMed  CAS  Google Scholar 

  • Westphal, J. R., Willems, H. W., Schalkwijk, C. J., Ruiter, D. J., and deWaal, R. M. (1993). A new 180-kDa dermal endothelial cell activation antigen: in vitro and in situ characteristics. J Invest Dermatol 100, 27–34.

    PubMed  CAS  Google Scholar 

  • Willett, C. G., Boucher, Y., di Tomaso, E., Duda, D. G., Munn, L. L., Tong, R. T., Chung, D. C., Sahani, D. V., Kalva, S. P., Kozin, S. V., et al. (2004). Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10, 145–147.

    PubMed  CAS  Google Scholar 

  • Willmann, J. K., Lutz, A. M., Paulmurugan, R., Patel, M. R., Chu, P., Rosenberg, J., and Gambhir, S. S. (2008). Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. Radiology 248, 936–944.

    PubMed  Google Scholar 

  • Winter, P. M., Caruthers, S. D., Kassner, A., Harris, T. D., Chinen, L. K., Allen, J. S., Lacy, E. K., Zhang, H., Robertson, J. D., Wickline, S. A., and Lanza, G. M. (2003). Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 63, 5838–5843.

    PubMed  CAS  Google Scholar 

  • Xu, J., Rodriguez, D., Kim, J. J., and Brooks, P. C. (2000). Generation of monoclonal antibodies to cryptic collagen sites by using subtractive immunization. Hybridoma 19, 375–385.

    PubMed  CAS  Google Scholar 

  • Xu, J., Rodriguez, D., Petitclerc, E., Kim, J. J., Hangai, M., Moon, Y. S., Davis, G. E., Brooks, P. C., and Yuen, S. M. (2001). Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J Cell Biol 154, 1069–1079.

    PubMed  CAS  Google Scholar 

  • Yankeelov, T. E., Niermann, K. J., Huamani, J., Kim, D. W., Quarles, C. C., Fleischer, A. C., Hallahan, D. E., Price, R. R., and Gore, J. C. (2006). Correlation between estimates of tumor perfusion from microbubble contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging. J Ultrasound Med 25, 487–497.

    PubMed  Google Scholar 

  • Zhu, A. X., Holalkere, N. S., Muzikansky, A., Horgan, K., and Sahani, D. V. (2008). Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma. Oncologist 13, 120–125.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, Departments of Surgery and Pharmacology, The Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX, 75390-8593, USA

    Rolf A. Brekken

Authors
  1. Grzegorz Korpanty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rolf A. Brekken
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rolf A. Brekken .

Editor information

Editors and Affiliations

  1. Cancer Institute, University College London, Huntlely St. 72, London, WC1E 6BT, United Kingdom

    Tim Meyer

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Korpanty, G., Brekken, R.A. (2010). Contrast Ultrasound in Imaging Tumor Angiogenesis. In: Meyer, T. (eds) Vascular Disruptive Agents for the Treatment of Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6609-4_8

Download citation

Publish with us

Policies and ethics

Search

Navigation