Abstract
Contrast-enhanced ultrasound (CEUS) imaging is a valuable tool for preclinical and clinical diagnostics. The most frequently used ultrasound contrast agents are microbubbles. Besides them, novel nano-sized materials are under investigation, which are briefly discussed in this chapter. For molecular CEUS, the ultrasound contrast agents are modified to actively target disease-associated molecular markers with a site-specific ligand. The most common markers for tumor imaging are related to neoangiogenesis, like the vascular endothelial growth factor receptor-2 (VEGFR2) and αvβ3 integrin. In this chapter, applications of molecular ultrasound to longitudinally monitor receptor expression during tumor growth, to detect neovascularization, and to evaluate therapy responses are described. Furthermore, we report on first clinical trials of molecular CEUS with VEGFR2-targeted phospholipid microbubbles showing promising results regarding patient safety and its ability to detect tumors of prostate, breast, and ovary. The chapter closes with an outlook on ultrasound theranostics, where (targeted) ultrasound contrast agents are used to increase the permeability of tumor tissues and to support drug delivery.
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References
Abou-Elkacem L, Bachawal SV, Willmann JK (2015) Ultrasound molecular imaging: Moving toward clinical translation. Eur J Radiol 84(9):1685–1693. https://doi.org/10.1016/j.ejrad.2015.03.016
Abou-Elkacem L, Wang H, Chowdhury SM, Kimura RH, Bachawal SV, Gambhir SS, Tian L, Willmann JK (2018) Thy1-targeted microbubbles for ultrasound molecular imaging of pancreatic ductal adenocarcinoma. Clin Cancer Res 24(7):1574–1585. https://doi.org/10.1158/1078-0432.CCR-17-2057
Abou-Elkacem L, Wilson KE, Johnson SM, Chowdhury SM, Bachawal S, Hackel BJ, Tian L, Willmann JK (2016) Ultrasound molecular imaging of the breast cancer neovasculature using engineered fibronectin scaffold ligands: a novel class of targeted contrast ultrasound agent. Theranostics 6(11):1740–1752. https://doi.org/10.7150/thno.15169
Adler DD, Carson PL, Rubin JM, Quinn-Reid D (1990) Doppler ultrasound color flow imaging in the study of breast cancer: preliminary findings. Ultrasound Med Biol 16(6):553–559
Anderson CR, Hu X, Zhang H, Tlaxca J, Decleves AE, Houghtaling R, Sharma K, Lawrence M, Ferrara KW, Rychak JJ (2011) Ultrasound molecular imaging of tumor angiogenesis with an integrin targeted microbubble contrast agent. Invest Radiol 46(4):215–224. https://doi.org/10.1097/RLI.0b013e3182034fed
Anderson CR, Rychak JJ, Backer M, Backer J, Ley K, Klibanov AL (2010) scVEGF microbubble ultrasound contrast agents: a novel probe for ultrasound molecular imaging of tumor angiogenesis. Invest Radiol 45(10):579–585. https://doi.org/10.1097/RLI.0b013e3181efd581
Arditi M, Frinking PJ, Zhou X, Rognin NG (2006) A new formalism for the quantification of tissue perfusion by the destruction-replenishment method in contrast ultrasound imaging. IEEE Trans Ultrason Ferroelectr Freq Control 53(6):1118–1129
Bachawal SV, Jensen KC, Lutz AM, Gambhir SS, Tranquart F, Tian L, Willmann JK (2013) Earlier detection of breast cancer with ultrasound molecular imaging in a transgenic mouse model. Cancer Res 73(6):1689–1698. https://doi.org/10.1158/0008-5472.CAN-12-3391
Bachawal SV, Jensen KC, Wilson KE, Tian L, Lutz AM, Willmann JK (2015) Breast cancer detection by B7-H3-Targeted ultrasound molecular imaging. Cancer Res 75(12):2501–2509. https://doi.org/10.1158/0008-5472.CAN-14-3361
Baetke SC, Rix A, Tranquart F, Schneider R, Lammers T, Kiessling F, Lederle W (2016) Squamous cell carcinoma xenografts: use of VEGFR2-targeted microbubbles for combined functional and molecular US to monitor antiangiogenic therapy effects. Radiology 278(2):430–440. https://doi.org/10.1148/radiol.2015142899
Barua A, Yellapa A, Bahr JM, Machado SA, Bitterman P, Basu S, Sharma S, Abramowicz JS (2014) Enhancement of ovarian tumor detection with alphavbeta3 integrin-targeted ultrasound molecular imaging agent in laying hens: a preclinical model of spontaneous ovarian cancer. Int J Gynecol Cancer 24(1):19–28. https://doi.org/10.1097/IGC.0000000000000040
Buchanan KD, Huang S, Kim H, Macdonald RC, McPherson DD (2008) Echogenic liposome compositions for increased retention of ultrasound reflectivity at physiologic temperature. J Pharm Sci 97(6):2242–2249. https://doi.org/10.1002/jps.21173
Bzyl J, Lederle W, Rix A, Grouls C, Tardy I, Pochon S, Siepmann M, Penzkofer T, Schneider M, Kiessling F, Palmowski M (2011) Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38). Eur Radiol 21(9):1988–1995. https://doi.org/10.1007/s00330-011-2138-y
Cebe-Suarez S, Zehnder-Fjallman A, Ballmer-Hofer K (2006) The role of VEGF receptors in angiogenesis; complex partnerships. Cell Mol Life Sci 63(5):601–615. https://doi.org/10.1007/s00018-005-5426-3
Chang EL, Ting CY, Hsu PH, Lin YC, Liao EC, Huang CY, Chang YC, Chan HL, Chiang CS, Liu HL, Wei KC, Fan CH, Yeh CK (2017) Angiogenesis-targeting microbubbles combined with ultrasound-mediated gene therapy in brain tumors. J Control Release 255:164–175. https://doi.org/10.1016/j.jconrel.2017.04.010
Cosgrove D, Harvey C (2009) Clinical uses of microbubbles in diagnosis and treatment. Med Biol Eng Comput 47(8):813–826. https://doi.org/10.1007/s11517-009-0434-3
Cui W, Bei J, Wang S, Zhi G, Zhao Y, Zhou X, Zhang H, Xu Y (2005) Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography. J Biomed Mater Res B Appl Biomater 73(1):171–178. https://doi.org/10.1002/jbm.b.30189
Dayton PA, Rychak JJ (2007) Molecular ultrasound imaging using microbubble contrast agents. Front Biosci 12:5124–5142
Deshpande N, Needles A, Willmann JK (2010) Molecular ultrasound imaging: current status and future directions. Clin Radiol 65(7):567–581. https://doi.org/10.1016/j.crad.2010.02.013
Deshpande N, Ren Y, Foygel K, Rosenberg J, Willmann JK (2011) Tumor angiogenic marker expression levels during tumor growth: longitudinal assessment with molecularly targeted microbubbles and US imaging. Radiology 258(3):804–811. https://doi.org/10.1148/radiol.10101079
Ellegala DB, Leong-Poi H, Carpenter JE, Klibanov AL, Kaul S, Shaffrey ME, Sklenar J, Lindner JR (2003) Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. Circulation 108(3):336–341. https://doi.org/10.1161/01.CIR.0000080326.15367.0C
Eschbach RS, Clevert DA, Hirner-Eppeneder H, Ingrisch M, Moser M, Schuster J, Tadros D, Schneider M, Kazmierczak PM, Reiser M, Cyran CC (2017) Contrast-enhanced ultrasound with VEGFR2-targeted microbubbles for monitoring regorafenib therapy effects in experimental colorectal adenocarcinomas in rats with DCE-MRI and immunohistochemical validation. PLoS ONE 12(1):e0169323. https://doi.org/10.1371/journal.pone.0169323
Ferrara K, Pollard R, Borden M (2007) Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. Annu Rev Biomed Eng 9:415–447. https://doi.org/10.1146/annurev.bioeng.8.061505.095852
Ferrara KW, Borden MA, Zhang H (2009) Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery. Acc Chem Res 42(7):881–892. https://doi.org/10.1021/ar8002442
Fix SM, Novell A, Yun Y, Dayton PA, Arena CB (2017) An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro. J Ther Ultrasound 5:7. https://doi.org/10.1186/s40349-017-0085-z
Fokong S, Fragoso A, Rix A, Curaj A, Wu Z, Lederle W, Iranzo O, Gatjens J, Kiessling F, Palmowski M (2013) Ultrasound molecular imaging of E-selectin in tumor vessels using poly n-butyl cyanoacrylate microbubbles covalently coupled to a short targeting peptide. Invest Radiol 48(12):843–850. https://doi.org/10.1097/RLI.0b013e31829d03ec
Fokong S, Siepmann M, Liu Z, Schmitz G, Kiessling F, Gatjens J (2011) Advanced characterization and refinement of poly N-butyl cyanoacrylate microbubbles for ultrasound imaging. Ultrasound Med Biol 37(10):1622–1634. https://doi.org/10.1016/j.ultrasmedbio.2011.07.001
Fouad YA, Aanei C (2017) Revisiting the hallmarks of cancer. Am J Cancer Res 7(5):1016–1036
Gao Y, Hernandez C, Yuan HX, Lilly J, Kota P, Zhou H, Wu H, Exner AA (2017) Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents. Nanomedicine 13(7):2159–2168. https://doi.org/10.1016/j.nano.2017.06.001
Hamilton AJ, Huang SL, Warnick D, Rabbat M, Kane B, Nagaraj A, Klegerman M, McPherson DD (2004) Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol 43(3):453–460. https://doi.org/10.1016/j.jacc.2003.07.048
Hitchcock KE, Caudell DN, Sutton JT, Klegerman ME, Vela D, Pyne-Geithman GJ, Abruzzo T, Cyr PE, Geng YJ, McPherson DD, Holland CK (2010) Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model. J Control Release 144(3):288–295. https://doi.org/10.1016/j.jconrel.2010.02.030
Hu Z, Yang B, Li T, Li J (2018) Thyroid cancer detection by ultrasound molecular imaging with SHP2-targeted perfluorocarbon nanoparticles. Contrast Media Mol Imaging 2018:8710862. https://doi.org/10.1155/2018/8710862
Huang SL, MacDonald RC (2004) Acoustically active liposomes for drug encapsulation and ultrasound-triggered release. Biochim Biophys Acta 1665(1–2):134–141. https://doi.org/10.1016/j.bbamem.2004.07.003
Ignee A, Atkinson NS, Schuessler G, Dietrich CF (2016) Ultrasound contrast agents. Endosc Ultrasound 5(6):355–362. https://doi.org/10.4103/2303-9027.193594
Kiessling F, Fokong S, Bzyl J, Lederle W, Palmowski M, Lammers T (2014) Recent advances in molecular, multimodal and theranostic ultrasound imaging. Adv Drug Deliv Rev 72:15–27. https://doi.org/10.1016/j.addr.2013.11.013
Kiessling F, Fokong S, Koczera P, Lederle W, Lammers T (2012) Ultrasound microbubbles for molecular diagnosis, therapy, and theranostics. J Nucl Med 53(3):345–348. https://doi.org/10.2967/jnumed.111.099754
Kiessling F, Huppert J, Palmowski M (2009) Functional and molecular ultrasound imaging: concepts and contrast agents. Curr Med Chem 16(5):627–642
Korpanty G, Carbon JG, Grayburn PA, Fleming JB, Brekken RA (2007) Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin Cancer Res 13(1):323–330. https://doi.org/10.1158/1078-0432.CCR-06-1313
Lanza GM, Wickline SA (2003) Targeted ultrasonic contrast agents for molecular imaging and therapy. Curr Probl Cardiol 28(12):625–653. https://doi.org/10.1016/j.cpcardiol.2003.11.001
Lee J, Min HS, You DG, Kim K, Kwon IC, Rhim T, Lee KY (2016) Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma. J Control Release 223:197–206. https://doi.org/10.1016/j.jconrel.2015.12.051
Leguerney I, Scoazec JY, Gadot N, Robin N, Penault-Llorca F, Victorin S, Lassau N (2015) Molecular ultrasound imaging using contrast agents targeting endoglin, vascular endothelial growth factor receptor 2 and integrin. Ultrasound Med Biol 41(1):197–207. https://doi.org/10.1016/j.ultrasmedbio.2014.06.014
Lentacker I, De Cock I, Deckers R, De Smedt SC, Moonen CT (2014) Understanding ultrasound induced sonoporation: definitions and underlying mechanisms. Adv Drug Deliv Rev 72:49–64. https://doi.org/10.1016/j.addr.2013.11.008
Li M, Luo H, Zhang W, He K, Chen Y, Liu J, Chen J, Wang D, Hao L, Ran H, Zheng Y, Wang Z, Li P (2018) Phase-shift, targeted nanoparticles for ultrasound molecular imaging by low intensity focused ultrasound irradiation. Int J Nanomedicine 13:3907–3920. https://doi.org/10.2147/IJN.S166200
Lindner JR, Dayton PA, Coggins MP, Ley K, Song J, Ferrara K, Kaul S (2000) Noninvasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles. Circulation 102(5):531–538
Liu C, Yan F, Xu Y, Zheng H, Sun L (2018) InVivo molecular ultrasound assessment of glioblastoma neovasculature with endoglin-targeted microbubbles. Contrast Media Mol Imaging 2018:8425495. https://doi.org/10.1155/2018/8425495
Liu J, Shang T, Wang F, Cao Y, Hao L, Ren J, Ran H, Wang Z, Li P, Du Z (2017) Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging. Int J Nanomedicine 12:911–923. https://doi.org/10.2147/IJN.S122667
Liu J, Xu F, Huang J, Xu J, Liu Y, Yao Y, Ao M, Li A, Hao L, Cao Y, Hu Z, Ran H, Wang Z, Li P (2018) Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery. Biomater Sci 6(11):2838–2849. https://doi.org/10.1039/c8bm00726h
Marshall D, Pedley RB, Boden JA, Boden R, Melton RG, Begent RH (1996) Polyethylene glycol modification of a galactosylated streptavidin clearing agent: effects on immunogenicity and clearance of a biotinylated anti-tumour antibody. Br J Cancer 73(5):565–572
Paefgen V, Doleschel D, Kiessling F (2015) Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery. Front Pharmacol 6:197. https://doi.org/10.3389/fphar.2015.00197
Palmowski M, Huppert J, Ladewig G, Hauff P, Reinhardt M, Mueller MM, Woenne EC, Jenne JW, Maurer M, Kauffmann GW, Semmler W, Kiessling F (2008) Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects. Mol Cancer Ther 7(1):101–109. https://doi.org/10.1158/1535-7163.MCT-07-0409
Palmowski M, Peschke P, Huppert J, Hauff P, Reinhardt M, Maurer M, Karger CP, Scholz M, Semmler W, Huber PE, Kiessling FM (2009) Molecular ultrasound imaging of early vascular response in prostate tumors irradiated with carbon ions. Neoplasia 11(9):856–863
Perera RH, Wu H, Peiris P, Hernandez C, Burke A, Zhang H, Exner AA (2017) Improving performance of nanoscale ultrasound contrast agents using N, N-Diethylacrylamide Stabilization. Nanomedicine 13(1):59–67. https://doi.org/10.1016/j.nano.2016.08.020
Pochon S, Tardy I, Bussat P, Bettinger T, Brochot J, von Wronski M, Passantino L, Schneider M (2010) BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol 45(2):89–95. https://doi.org/10.1097/RLI.0b013e3181c5927c
Postema M, Schmitz G (2007) Ultrasonic bubbles in medicine: influence of the shell. Ultrason Sonochem 14(4):438–444. https://doi.org/10.1016/j.ultsonch.2006.09.013
Pysz MA, Guracar I, Tian L, Willmann JK (2012) Fast microbubble dwell-time based ultrasonic molecular imaging approach for quantification and monitoring of angiogenesis in cancer. Quant Imaging Med Surg 2(2):68–80. https://doi.org/10.3978/j.issn.2223-4292.2012.06.05
Pysz MA, Machtaler SB, Seeley ES, Lee JJ, Brentnall TA, Rosenberg J, Tranquart F, Willmann JK (2015) Vascular endothelial growth factor receptor type 2-targeted contrast-enhanced US of pancreatic cancer neovasculature in a genetically engineered mouse model: potential for earlier detection. Radiology 274(3):790–799. https://doi.org/10.1148/radiol.14140568
Reinhardt M, Hauff P, Briel A, Uhlendorf V, Linker RA, Maurer M, Schirner M (2005) Sensitive particle acoustic quantification (SPAQ): a new ultrasound-based approach for the quantification of ultrasound contrast media in high concentrations. Invest Radiol 40(1):2–7
Rix A, Lederle W, Theek B, Lammers T, Moonen C, Schmitz G, Kiessling F (2018) Advanced ultrasound technologies for diagnosis and therapy. J Nucl Med 59(5):740–746. https://doi.org/10.2967/jnumed.117.200030
Schroeder A, Kost J, Barenholz Y (2009) Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes. Chem Phys Lipids 162(1–2):1–16. https://doi.org/10.1016/j.chemphyslip.2009.08.003
Smeenge M, Tranquart F, Mannaerts CK, de Reijke TM, van de Vijver MJ, Laguna MP, Pochon S, de la Rosette J, Wijkstra H (2017) First-in-human ultrasound molecular imaging with a VEGFR2-specific ultrasound molecular contrast agent (BR55) in prostate cancer: a safety and feasibility pilot study. Invest Radiol 52(7):419–427. https://doi.org/10.1097/RLI.0000000000000362
Sorace AG, Saini R, Mahoney M, Hoyt K (2012) Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy. J Ultrasound Med 31(10):1543–1550
Spivak I, Rix A, Schmitz G, Fokong S, Iranzo O, Lederle W, Kiessling F (2016) Low-dose molecular ultrasound imaging with E-selectin-targeted PBCA microbubbles. Mol Imaging Biol 18(2):180–190. https://doi.org/10.1007/s11307-015-0894-9
Tardy I, Pochon S, Theraulaz M, Emmel P, Passantino L, Tranquart F, Schneider M (2010) Ultrasound molecular imaging of VEGFR2 in a rat prostate tumor model using BR55. Invest Radiol 45(10):573–578. https://doi.org/10.1097/RLI.0b013e3181ee8b83
Tsuruta JK, Klauber-DeMore N, Streeter J, Samples J, Patterson C, Mumper RJ, Ketelsen D, Dayton P (2014) Ultrasound molecular imaging of secreted frizzled related protein-2 expression in murine angiosarcoma. PLoS ONE 9(1):e86642. https://doi.org/10.1371/journal.pone.0086642
Unnikrishnan S, Klibanov AL (2012) Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application. AJR Am J Roentgenol 199(2):292–299. https://doi.org/10.2214/AJR.12.8826
Wang S, Herbst EB, Mauldin FW Jr, Diakova GB, Klibanov AL, Hossack JA (2016) Ultra-low-dose ultrasound molecular imaging for the detection of angiogenesis in a mouse murine tumor model: how little can we see? Invest Radiol 51(12):758–766. https://doi.org/10.1097/RLI.0000000000000310
Warram JM, Sorace AG, Saini R, Umphrey HR, Zinn KR, Hoyt K (2011) A triple-targeted ultrasound contrast agent provides improved localization to tumor vasculature. J Ultrasound Med 30(7):921–931
Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S (1998) Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 97(5):473–483
Willmann JK, Bonomo L, Carla Testa A, Rinaldi P, Rindi G, Valluru KS, Petrone G, Martini M, Lutz AM, Gambhir SS (2017) Ultrasound molecular imaging With BR55 in patients with breast and ovarian lesions: first-in-human results. J Clin Oncol 35(19):2133–2140. https://doi.org/10.1200/JCO.2016.70.8594
Willmann JK, Kimura RH, Deshpande N, Lutz AM, Cochran JR, Gambhir SS (2010) Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast microbubbles conjugated to integrin-binding knottin peptides. J Nucl Med 51(3):433–440. https://doi.org/10.2967/jnumed.109.068007
Willmann JK, Lutz AM, Paulmurugan R, Patel MR, Chu P, Rosenberg J, Gambhir SS (2008) Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo. Radiology 248(3):936–944. https://doi.org/10.1148/radiol.2483072231
Yang H, Cai W, Xu L, Lv X, Qiao Y, Li P, Wu H, Yang Y, Zhang L, Duan Y (2015) Nanobubble-Affibody: novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor. Biomaterials 37:279–288. https://doi.org/10.1016/j.biomaterials.2014.10.013
Yang L, Cheng J, Chen Y, Yu S, Liu F, Sun Y, Chen Y, Ran H (2017) Phase-transition nanodroplets for real-time photoacoustic/ultrasound dual-modality imaging and photothermal therapy of sentinel lymph node in breast cancer. Sci Rep 7:45213. https://doi.org/10.1038/srep45213. https://www.nature.com/articles/srep45213#supplementary-information
Yuan HX, Wang WP, Wen JX, Lin LW, Exner AA, Guan PS, Chen XJ (2018) Dual-targeted microbubbles specific to integrin alphaVbeta3 and vascular endothelial growth factor receptor 2 for ultrasonography evaluation of tumor angiogenesis. Ultrasound Med Biol 44(7):1460–1467. https://doi.org/10.1016/j.ultrasmedbio.2018.03.022
Zafarnia S, Bzyl-Ibach J, Spivak I, Li Y, Koletnik S, Doleschel D, Rix A, Pochon S, Tardy I, Koyadan S, van Zandvoort M, Palmowski M, Kiessling F, Lederle W (2017) Nilotinib enhances tumor angiogenesis and counteracts VEGFR2 blockade in an orthotopic breast cancer xenograft model with desmoplastic response. Neoplasia 19(11):896–907. https://doi.org/10.1016/j.neo.2017.08.009
Zhang H, Ingham ES, Gagnon MK, Mahakian LM, Liu J, Foiret JL, Willmann JK, Ferrara KW (2017) In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles. Biomaterials 118:63–73. https://doi.org/10.1016/j.biomaterials.2016.11.026
Zhang H, Tam S, Ingham ES, Mahakian LM, Lai CY, Tumbale SK, Teesalu T, Hubbard NE, Borowsky AD, Ferrara KW (2015) Ultrasound molecular imaging of tumor angiogenesis with a neuropilin-1-targeted microbubble. Biomaterials 56:104–113. https://doi.org/10.1016/j.biomaterials.2015.03.043
Zhou J, Wang H, Zhang H, Lutz AM, Tian L, Hristov D, Willmann JK (2016) VEGFR2-targeted three-dimensional ultrasound imaging can predict responses to antiangiogenic therapy in preclinical models of colon cancer. Cancer Res 76(14):4081–4089. https://doi.org/10.1158/0008-5472.CAN-15-3271
Zlitni A, Gambhir SS (2018) Molecular imaging agents for ultrasound. Curr Opin Chem Biol 45:113–120. https://doi.org/10.1016/j.cbpa.2018.03.017
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Baier, J., Rix, A., Kiessling, F. (2020). Molecular Ultrasound Imaging. In: Schober, O., Kiessling, F., Debus, J. (eds) Molecular Imaging in Oncology. Recent Results in Cancer Research, vol 216. Springer, Cham. https://doi.org/10.1007/978-3-030-42618-7_15
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