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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-08-2010

Contrast-enhanced ultrasound for molecular imaging of angiogenesis

Authors: J. R. Eisenbrey, F. Forsberg

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Special Issue 1/2010

Abstract

Introduction

Molecular imaging of angiogenesis using contrast-enhanced ultrasound allows for functional, real-time, inexpensive imaging of angiogenesis. The addition of stabilized microbubbles as contrast agents greatly improves ultrasound signal to noise ratio/signal strength/image quality (up to 25 dB) and allows for imaging of angiogenic vasculature.

Methods

In this article recent advances in the usage of contrast-enhanced ultrasound for molecular imaging of angiogenesis are reviewed.

Results

The usage of commercially available agents and correlations between their imaging parameters and molecular markers of angiogenesis are reviewed. Recent developments in ultrasound contrast agents targeted to angiogenic markers for both diagnosis and monitoring are discussed. Finally, a brief overview of the emerging field of chemotherapeutic-loaded agents, which can be used with ultrasound-triggered drug delivery, is provided.

Makrilia N, Lappa T, Xyla V, Nikolaidis I, Syrigos K. The role of angiogenesis in solid tumours: an overview. Eur J Intern Med 2009;20:663–71.CrossRefPubMed

Goldberg BB, Raichlen JS, Forsberg F. Ultrasound contrast agents: basic principles and clinical applications. 2nd ed. London: Martin Dunitz; 2001.

Forsberg F, Dicker AP, Thakur ML, Rawool NM, Liu JB, Shi WT, et al. Comparing contrast-enhanced ultrasound to immunohistochemical markers of angiogenesis in a human melanoma xenograft model: preliminary results. Ultrasound Med Biol 2002;28:445–51.CrossRefPubMed

Forsberg F, Kuruvilla B, Pascua MB, Chaudhari MH, Merton DA, Palazzo JP, et al. Comparing contrast-enhanced color flow imaging and pathological measures of breast lesion vascularity. Ultrasound Med Biol 2008;34:1365–72.CrossRefPubMed

Ro RJ, Forsberg F, Liu JB, Fox TB, Potoczek M, Chiou SY, Lewin PA, Goldberg BB. Assessing angiogenesis in murine glioma and breast tumor models with contrast-enhanced ultrasound imaging. Proc IEEE US Symp 2006:416–19.

Fleicher AC. Sonographic depiction of tumor vascularity and flow: from in vivo models to clinical applications. J Ultrasound Med 2000;19:55–61.

Schroeder RJ, Hauff P, Bartels T, Vogel K, Jeschke J, Hidajat N, et al. Tumor vascularization in experimental melanomas: correlation between unenhanced and contrast enhanced power Doppler imaging and histological grading. Ultrasound Med Biol 2001;27:761–71.CrossRefPubMed

Linden RA, Trabulsi EJ, Forsberg F, Gittens PR, Gomella LJ, Halpern EJ. Contrast enhanced ultrasound flash replenishment method for directed prostate biopsies. J Urol 2007;178:2354–8.CrossRefPubMed

Sugimoto K, Moriyasu F, Kamiyama N, Metoki R, Yamada M, Imai Y, et al. Analysis of morphological vascular changes of hepatocellular carcinoma by microflow imaging using contrast-enhanced sonography. Hepatol Res 2008;38:790–9.CrossRefPubMed

10.

Wilson SR, Jang HJ, Kim TK, Iijima H, Kamiyama N, Burns PN. Real-time temporal maximum-intensity-projection imaging of hepatic lesions with contrast-enhanced sonography. AJR Am J Roentgenol 2008;190(3):691–5.CrossRefPubMed

11.

Iordanescu I, Becker C, Zetter B, Dunning P, Taylor GA. Tumor vascularity: evaluation in a murine model with contrast-enhanced color Doppler US—effect of angiogenesis inhibitors. Radiology 2002;222:460–7.CrossRefPubMed

12.

Krix M, Kiessling F, Vosseler S, Kiessling I, Le-Huu M, Fusenig NE, et al. Comparison of intermittent-bolus contrast imaging with conventional power Doppler sonography: quantification of tumor perfusion in small animals. Ultrasound Med Biol 2003;29:1093–103.CrossRefPubMed

13.

Niermann KJ, Fleischer AC, Huamani J, Yankeelov TE, Kim DW, Wilson WD, et al. 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 2007;26:749–56.PubMed

14.

Pollard RE, Broumas AR, Wisner ER, Vekich SV, Ferrara KW. Quantitative contrast enhanced ultrasound and CT assessment of tumor response to antiangiogenic therapy in rats. Ultrasound Med Biol 2007;33:235–45.CrossRefPubMed

15.

Ro RJ, Forsberg F, Liu JB, Chiou SY, Merton DA, Lipcan KJ, Potoczek M, Dicker AP, Nazarian LN. Contrast enhanced US for monitoring the effect of VEGF Trap on melanoma tumor vascularity. Proc IEEE Ultrason Symp, 1977–1980, 2007.

16.

Guibal A, Taillade L, Mulé S, Comperat E, Badachia Y, Golmard JL, et al. Noninvasive contrast-enhanced US quantitative assessment of tumor microcirculation in a murine model: effect of discontinuing anti-VEGF therapy. Radiology 2010;254:420–9.CrossRefPubMed

17.

Dickson PV, Hamner JB, Sims TL, Fraga CH, Ng CY, Rajasekeran S, et al. Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res 2007;13:3942–50.CrossRefPubMed

18.

Forsberg F, Ro R, Potoczek M, Liu JB, James KM, Dicker AP, et al. Assessment of angiogenesis: implications for ultrasound imaging. Ultrasonics 2004;42:325–30.CrossRefPubMed

19.

Lassau N, Koscielny S, Albiges L, Chami L, Benatsou B, Chebil M, et al. Metastatic renal cell carcinoma treated with sunitinib: early evaluation of treatment response using dynamic contrast-enhanced ultrasonography. Clin Cancer Res 2010;16:1216–25.CrossRefPubMed

20.

Averkiou M, Lampaskis M, Kyriakopoulou K, Skarlos D, Klouvas G, Strouthos C, et al. Quantification of tumor microvascularity with respiratory gated contrast enhanced ultrasound for monitoring therapy. Ultrasound Med Biol 2010;36:68–77.CrossRefPubMed

21.

Cosgrove DO, Lassua N. Ultrasound perfusion imaging of angiogenesis. Eur J Nucl Med Mol Imaging 2010; In press.

22.

Du J, Li FH, Fang H, Xia JG, Zhu CX. Correlation of real-time gray scale contrast-enhanced ultrasonography with microvessel density and vascular endothelial growth factor expression for assessment of angiogenesis in breast lesions. J Ultrasound Med 2008;27:821–31.PubMed

23.

Huber S, Vesely M, Zuna I, Delorme S, Czembirek H. Fibroadenomas: computer-assisted quantitative evaluation of contrast-enhanced power Doppler features and correlation with histopathology. Ultrasound Med Biol 2001;27:3–11.CrossRefPubMed

24.

Yang WT, Tse GMK, Lam PKW, Metreweli C, Chang J. Correlation between color power Doppler sonographic measurement of tumor vasculature and immunohistochemical analysis of microvessel density for the quantitation of angiogenesis. J Ultrasound Med 2002;21:1227–35.PubMed

25.

Leong-Poi H. Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy. Cardiovasc Res 2009;84:190–200.CrossRefPubMed

26.

Villanueva FS, Wagner WR. Ultrasound molecular imaging of cardiovascular disease. Nat Clin Pract Cardiovasc Med 2008;5:S26–32.CrossRefPubMed

27.

Coppolino D, Dedhar S. Bi-directional signal transduction by integrin receptors. Int J Biochem Cell Biol 2000;32:171–88.CrossRefPubMed

28.

Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994;264:569–71.CrossRefPubMed

29.

Dayton PA, Pearson D, Clark J, Simon S, Schumann PA, Zutshi R, et al. Ultrasonic analysis of peptide- and antibody-targeted microbubble contrast agents for molecular imaging of alphavbeta3-expressing cells. Mol Imaging 2004;3:125–34.CrossRefPubMed

30.

Wheatley MA, Lathia JD, Oum KL. Polymeric ultrasound contrast agent targeted to integrins: importance of process methods and surface density of ligands. Biomacromolecules 2007;8:516–22.CrossRefPubMed

31.

Leong-Poi H, Christiansen J, Klibanov AL, Kaul S, Lindner JR. Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 2003;107:455–60.CrossRefPubMed

32.

Weller GER, Wong MKK, Modzelewski RA, Lu E, Klibanov A, Wagner WR, et al. Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res 2005;65:533–9.PubMed

33.

Willmann JK, Kimura RH, Deshpande N, Lutz AM, Cochran JR, Gambhir SS. Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast microbubbles conjugated to integrin-binding knottin peptides. J Nucl Med 2010;51:433–40.CrossRefPubMed

34.

Lathia JD, Leodore L, Wheatley MA. Polymeric contrast agent with targeting potential. Ultrasonics 2004;42:763–8.CrossRefPubMed

35.

Leong-Poi H, Christiansen J, Heppner P, Lewis CW, Klibanov AL, Kaul S, et al. Assessment of endogenous and therapeutic arteriogenesis by contrast ultrasound molecular imaging of integrin expression. Circulation 2005;111:3248–54.CrossRefPubMed

36.

Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249–57.CrossRefPubMed

37.

Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 2004;56:1649–59.CrossRefPubMed

38.

Lyshchik A, Fleisher AC, Huamani J, Hallahan DE, Brissova M, Gore JC. Molecular imaging of vascular endothelial growth factor receptor 2 expression using targeted contrast-enhanced high-frequency ultrasonography. J Ultrasound Med 2007;26:1575–86.PubMed

39.

Korpanty G, Carbon JG, Grayburn PA, Fleming JB, Brekken RA. Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin Cancer Res 2007;13:323–30.CrossRefPubMed

40.

Willmann JK, Lutz AM, Paulmurugan R, Patel MR, Chu P, Rosenberg J, et al. Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. Radiology 2008;248:936–44.CrossRefPubMed

41.

Rychak JJ, Graba J, Cheung AM, Mystry BS, Lindner JR, Kerbel RS, et al. Microultrasound molecular imaging of vascular endothelial growth factor receptor 2 in a mouse model of tumor angiogenesis. Mol Imaging 2007;6:289–96.PubMed

42.

Palmowski M, Huppert J, Ladewig G, Hauff P, Reinhardt M, Mueller MM, et al. Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects. Mol Cancer Ther 2008;7:101–9.CrossRefPubMed

43.

Okahara H, Yagita H, Miyake K, Okumura K. Involvement of very late activation antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) in tumor necrosis factor alpha enhancement of experimental metastasis. Cancer Res 1994;54:3233–36.PubMed

44.

Molema G, de Leij LFMH, Meijer DKF. Tumor vascular endothelium: barrier or target in tumor directed drug delivery and immunotherapy. Pharm Res 1997;14:2–10.CrossRefPubMed

45.

Behm CZ, Kaufmann BA, Carr C, Lankford M, Sanders JM, Rose CE, et al. Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation 2008;117:2902–11.CrossRefPubMed

46.

Hamilton AJ, Huang SL, Warnick D, Rabbat M, Kane B, Nagaraj A, et al. Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol 2004;43:453–60.CrossRefPubMed

47.

Klibanov AL. Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging. Adv Drug Deliv Rev 1999;37:139–57.CrossRefPubMed

48.

Bekeredjian R, Katus HA, Kuecherer HF. Therapeutic use of ultrasound targeted microbubble destruction: a review of non-cardiac applications. Ultraschall Med 2006;27:134–40.CrossRefPubMed

49.

Dijkmans PA, Juffermans LJM, Musters RJP, van Wamel A, ten Cate FJ, van Gilst W, et al. Microbubbles and ultrasound: from diagnosis to therapy. Eur J Echocardiogr 2004;5:245–56.CrossRefPubMed

50.

Hernot S, Klibanov AL. Microbubbles in ultrasound-triggered drug and gene delivery. Adv Drug Deliv Rev 2008;60:1153–66.CrossRefPubMed

51.

Ferrara K, Pollard R, Borden M. Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. Annu Rev Biomed Eng 2007;9:415–47.CrossRefPubMed

52.

Unger EC, McCreery TP, Sweitzer RH, Caldwell VE, Wu Y. Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent. Invest Radiol 1998;33:886–92.CrossRefPubMed

53.

Tiukinhoy-Laing SD, Huang S, Klegerman M, Holland CK, McPherson DD. Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes. Thromb Res 2007;119:777–84.CrossRefPubMed

54.

Borden MA, Caskey CH, Little E, Gillies RJ, Ferrara KW. DNA and polylysine adsorption and multilayer construction onto cationic lipid-coated microbubbles. Langmuir 2007;23:9401–8.CrossRefPubMed

55.

Howard CM, Forsberg F, Minimo C, Liu JB, Merton DA, Claudio PP. Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents. J Cell Physiol 2006;209:413–21.CrossRefPubMed

56.

Tinkov S, Winter G, Coester C, Bekeredjian R. New doxorubicin-loaded phospholipids microbubbles for targeted tumor therapy: part I—formulation development and in-vitro characterization. J Control Release 2010;143:143–50.CrossRefPubMed

57.

Kang J, Wu X, Wang Z, Ran H, Xu C, Wu J, et al. Antitumor effect of docetaxel-loaded lipid microbubbles combined with ultrasound-targeted microbubble activation on VX2 rabbit liver tumors. J Ultrasound Med 2010;29:61–70.PubMed

58.

Lentacker I, Geers B, Demeester J, De Smedt SC, Sanders NN. Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved. Mol Ther 2010;18:101–8.CrossRefPubMed

59.

Shi WT, Böhmer MR, Emmer M et al. Ultrasound therapy with drug loaded microcapsules. Proc IEEE US Symp 2007; 773–6.

60.

Gao ZH, Fain HD, Rapoport N. Controlled and targeted tumor chemotherapy by micellar-encapsulated drug and ultrasound. J Control Release 2005;102:203–22.CrossRefPubMed

61.

Eisenbrey JR, Burstein OM, Kambhampati R, Forsberg F, Liu JB, Wheatley MA. Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery. J Control Release 2010;143:38–44.CrossRefPubMed

62.

Eisenbrey JR, Soulen MC, Wheatley MA. Delivery of encapsulated doxorubicin by ultrasound-mediated size reduction of drug-loaded polymer contrast agents. IEEE Trans Biomed Eng 2010;57:24–8.CrossRefPubMed

Title: Contrast-enhanced ultrasound for molecular imaging of angiogenesis
Authors: J. R. Eisenbrey
F. Forsberg
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue Special Issue 1/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-010-1449-6

2024 ASCO Annual Meeting

Springer Medicine

Contrast-enhanced ultrasound for molecular imaging of angiogenesis

Abstract

Introduction

Methods

Results

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Introduction

Methods

Results

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