Therapeutic Use of Ultrasound Targeted Microbubble Destruction: A Review of Non-Cardiac Applications

Zusammenfassung

Die Entwicklung von Ultraschallkontrastmitteln der zweiten Generation hat zu einer Erweiterung der diagnostischen Optionen in der Ultraschalldiagnostik geführt. Ihre physikalischen Eigenschaften erlauben auch einen therapeutischen Einsatz. So konnte gezeigt werden, dass die ultraschallgesteuerte Zerstörung von gasgefüllten Mikrosphären für die organspezifische Freisetzung von gentherapeutischen Vektoren und Medikamenten genutzt werden kann. Die meisten Anwendungen auf diesem Gebiet wurden bislang am Herzen getestet. Allerdings ist dieses nicht-invasive Verfahren auf alle Organe übertragbar, die dem Ultraschall zugänglich sind. In dieser Übersichtsarbeit sollen die theoretischen Hintergründe dieser Methode sowie die nichtkardialen Applikationen beschrieben werden.

Abstract

The development of second generation ultrasound contrast agents has extended the diagnostic scope of ultrasound imaging. Due to their physical characteristics, a therapeutic application of such microbubble based contrast agents has been promoted. Recently, several groups have demonstrated that ultrasound targeted microbubble destruction (UTMD) may deliver drugs or gene therapy vectors to organs accessible by ultrasound, thus providing a new technique for non-invasive, organ specific delivery of bioactive substances. Most applications in this field have been tested in cardiac models, but other organs can be treated as well. This article will give an overview of the background of UTMD and its non-cardiac applications.

Kontrastmittel - Ultraschall - Medikamententherapie - Gentherapie - Echolardiographie

Contrast agents - ultrasound - drug therapy - gene therapy - echocardiography

References

• 1 Shohet R V, Chen S, Zhou Y T. et al . Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium.  Circulation. 2000;  101 2554-2556
• 2 Mukherjee D, Wong J, Griffin B. et al . Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration.  J Am Coll Cardiol. 2000;  35 1678-1686
• 3 Chen S, Shohet R V, Bekeredjian R. et al . Optimization of ultrasound parameters for cardiac gene delivery of adenoviral or plasmid deoxyribonucleic acid by ultrasound-targeted microbubble destruction.  J Am Coll Cardiol. 2003;  42 301-308
• 4 Bekeredjian R, Chen S, Frenkel P A. et al . Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart.  Circulation. 2003;  108 1022-1026
• 5 Keller M W, Feinstein S B, Watson D D. Successful left ventricular opacification following peripheral venous injection of sonicated contrast agent: an experimental evaluation.  Am Heart J. 1987;  114 570-575
• 6 Mayer S, Grayburn P A. Myocardial contrast agents: recent advances and future directions.  Prog Cardiovasc Dis. 2001;  44 33-44
• 7 Von Bibra H, Voigt J U, Froman M. et al . Interaction of Microbubbles with Ultrasound.  Echocardiography. 1999;  16 733-741
• 8 Albrecht T, Blomley M, Bolondi L. et al . EFSUMB Study Group. Guidelines for the use of contrast agents in ultrasound.  Ultraschall Med. 2004;  25 249-256
• 9 Firschke C, Lindner J R, Wei K. et al . Myocardial perfusion imaging in the setting of coronary artery stenosis and acute myocardial infarction using venous injection of a second-generation echocardiographic contrast agent.  Circulation. 1997;  96 959-967
• 10 Becher H, Tiemann K, Schlief R. et al . Harmonic Power Doppler Contrast Echocardiography: Preliminary Clinical Results.  Echocardiography. 1997;  14 637
• 11 Burns P N, Wilson S R, Simpson D H. Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast.  Invest Radiol. 2000;  35 58-71
• 12 Strobel D, Kleinecke C, Hansler J. et al . Contrast-enhanced sonography for the characterisation of hepatocellular carcinomas-correlation with histological differentiation.  Ultraschall Med. 2005;  26 270-276
• 13 Wei K, Jayaweera A R, Firoozan S. et al . Basis for detection of stenosis using venous administration of microbubbles during myocardial contrast echocardiography: bolus or continuous infusion?.  J Am Coll Cardiol. 1998;  32 252-260
• 14 Leong-Poi H, Le E, Rim S J. et al . Quantification of myocardial perfusion and determination of coronary stenosis severity during hyperemia using real-time myocardial contrast echocardiography.  J Am Soc Echocardiogr. 2001;  14 1173-1182
• 15 Hansen A, Bekeredjian R, Filusch A. et al . Cardioprotective effects of the novel selective endothelin-A receptor antagonist BSF 461 314 in ischemia-reperfusion injury.  J Am Soc Echocardiogr. 2005;  18 1213-1220
• 16 Frenkel P A, Chen S, Thai T. et al . DNA-loaded albumin microbubbles enhance ultrasound-mediated transfection in vitro.  Ultrasound Med Biol. 2002;  28 817-822
• 17 Pislaru S V, Pislaru C, Kinnick R R. et al . Optimization of ultrasound-mediated gene transfer: comparison of contrast agents and ultrasound modalities.  Eur Heart J. 2003;  24 1690-1698
• 18 Price R J, Skyba D M, Kaul S. et al . Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound.  Circulation. 1998;  98 1264-1267
• 19 Bekeredjian R, Chen S, Grayburn P A. et al . Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction.  Ultrasound Med Biol. 2005;  31 687-691
• 20 Christiansen J P, French B A, Klibanov A L. et al . Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles.  Ultrasound Med Biol. 2003;  29 1759-1767
• 21 Korpanty G, Chen S, Shohet R V. et al . Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles.  Gene Ther. 2005;  [Epub ahead of print]
• 22 Huber P E, Pfisterer P. In vitro and in vivo transfection of plasmid DNA in the Dunning prostate tumor R3327-AT1 is enhanced by focused ultrasound.  Gene Ther. 2000;  7 1516-1525
• 23 Miller D L, Bao S, Gres R A. et al . Ultrasonic enhancement of gene transfection in murine melanoma tumors.  Ultrasound Med Biol. 1999;  25 1425-1430
• 24 Emlen W, Mannik M. Kinetics and mechanisms for removal of circulating single-stranded DNA in mice.  J Exp Med. 1978;  147 684-699
• 25 Postema M, van Wamel A, Lancee C T. et al . Ultrasound-induced encapsulated microbubble phenomena.  Ultrasound Med Biol. 2004;  30 827-840
• 26 Brujan E A. The role of cavitation microjets in the therapeutic applications of ultrasound.  Ultrasound Med Biol. 2004;  30 381-387
• 27 Tachibana K, Uchida T, Ogawa K. et al . Induction of cell-membrane porosity by ultrasound.  Lancet. 1999;  353 1409
• 28 Bao S, Thrall B D, Miller D L. Transfection of a reporter plasmid into cultured cells by sonoporation in vitro.  Ultrasound Med Biol. 1997;  23 953-957
• 29 Miller D L, Quddus J. Sonoporation of monolayer cells by diagnostic ultrasound activation of contrast agent gas bodies.  Ultrasound Med Biol. 2000;  26 661-667
• 30 Miller D L, Pislaru S V, Greenleaf J E. Sonoporation: mechanical DNA delivery by ultrasonic cavitation.  Somat Cell Mol Genet. 2002;  27 115-134
• 31 Marmottant P, Hilgenfeldt S. Controlled vesicle deformation and lysis by single oscillating bubbles.  Nature. 2003;  423 153-156
• 32 van Wamel A, Bouakaz A, Versluis M. et al . Micromanipulation of endothelial cells: ultrasound-microbubble-cell interaction.  Ultrasound Med Biol. 2004;  30 1255-1258
• 33 Zhu S, Zhong P. Shock-wave-inertial microbubble interaction: a theoretical study based on the Gilmore formulation for bubble dynamics.  J Acoust Soc Am. 1999;  106 3024-3033
• 34 Zhong P, Lin H, Xi X. et al . Shock wave-inertial microbubble interaction: methodology, physical characterization, and bioeffect study.  J Acoust Soc Am. 1999;  105 1997-2009
• 35 Holt R G, Roy R A. Measurements of bubble-enhanced heating from focused, MHz-frequency ultrasound in a tissue-mimicking material.  Ultrasound Med Biol. 2001;  27 1399-1412
• 36 Stride E, Saffari N. On the destruction of microbubble ultrasound contrast agents.  Ultrasound Med Biol. 2003;  29 563-573
• 37 May D J, Allen J S, Ferrara K W. Dynamics and fragmentation of thick-shelled microbubbles.  IEEE Trans Ultrason Ferroelectr Freq Control. 2002;  49 1400-1410
• 38 Bouakaz A, Versluis M, de Jong N. High-speed optical observations of contrast agent destruction.  Ultrasound Med Biol. 2005;  31 391-399
• 39 Lawrie A, Brisken A F, Francis S E. et al . Microbubble-enhanced ultrasound for vascular gene delivery.  Gene Ther. 2000;  7 2023-2027
• 40 Lawrie A, Brisken A F, Francis S E. et al . Ultrasound-enhanced transgene expression in vascular cells is not dependent upon cavitation-induced free radicals.  Ultrasound Med Biol. 2003;  29 1453-1461
• 41 Teupe C, Richter S, Fisslthaler B. et al . Vascular gene transfer of phosphomimetic endothelial nitric oxide synthase (S1177D) using ultrasound-enhanced destruction of plasmid-loaded microbubbles improves vasoreactivity.  Circulation. 2002;  105 1104-1109
• 42 Akowuah E F, Gray C, Lawrie A. et al . Ultrasound-mediated delivery of TIMP-3 plasmid DNA into saphenous vein leads to increased lumen size in a porcine interposition graft model.  Gene Ther. 2005;  [Epub ahead of print]
• 43 Taniyama Y, Tachibana K, Hiraoka K. et al . Local delivery of plasmid DNA into rat carotid artery using ultrasound.  Circulation. 2002;  105 1233-1239
• 44 Hashiya N, Aoki M, Tachibana K. et al . Local delivery of E2F decoy oligodeoxynucleotides using ultrasound with microbubble agent (Optison) inhibits intimal hyperplasia after balloon injury in rat carotid artery model.  Biochem Biophys Res Commun. 2004;  317 508-514
• 45 Hajri Z, Boukadoum M, Hamam H. et al . An investigation of the physical forces leading to thrombosis disruption by cavitation.  J Thromb Thrombolysis. 2005;  20 27-32
• 46 Culp W C, Porter T R, Xie F. et al . Microbubble potentiated ultrasound as a method of declotting thrombosed dialysis grafts: experimental study in dogs.  Cardiovasc Intervent Radiol. 2001;  24 407-412
• 47 Culp W C, Porter T R, McCowan T C. et al . Microbubble-augmented ultrasound declotting of thrombosed arteriovenous dialysis grafts in dogs.  J Vasc Interv Radiol. 2003;  14 343-347
• 48 Xie F, Tsutsui J M, Lof J. et al . Effectiveness of lipid microbubbles and ultrasound in declotting thrombosis.  Ultrasound Med Biol. 2005;  31 979-985
• 49 Dhond M R, Nguyen T T, Dolan C. et al . Ultrasound-enhanced thrombolysis at 20 kHz with air-filled and perfluorocarbon-filled contrast bispheres.  J Am Soc Echocardiogr. 2000;  13 1025-1029
• 50 Tachibana K, Tachibana S. Albumin microbubble echo-contrast material as an enhancer for ultrasound accelerated thrombolysis.  Circulation. 1995;  92 1148-1150
• 51 Mizushige K, Kondo I, Ohmori K. et al . Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure.  Ultrasound Med Biol. 1999;  25 1431-1437
• 52 Liang H D, Lu Q L, Xue S A. et al . Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells.  Ultrasound Med Biol. 2004;  30 1523-1529
• 53 Lu Q L, Liang H D, Partridge T. et al . Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage.  Gene Ther. 2003;  10 396-405
• 54 Wang X, Liang H D, Dong B. et al . Gene transfer with microbubble ultrasound and plasmid DNA into skeletal muscle of mice: comparison between commercially available microbubble contrast agents.  Radiology. 2005;  237 224-229
• 55 Taniyama Y, Tachibana K, Hiraoka K. et al . Development of safe and efficient novel nonviral gene transfer using ultrasound: enhancement of transfection efficiency of maked plasmid DNA in skeletal muscle.  Gene Ther. 2002;  9 372-380
• 56 Song J, Qi M, Kaul S. et al . Stimulation of arteriogenesis in skeletal muscle by microbubble destruction with ultrasound.  Circulation. 2002;  106 1550-1555
• 57 Song J, Cottler P S, Klibanov A L. et al . Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction.  Am J Physiol Heart Circ Physiol. 2004;  287 H2754-2761
• 58 Sheikov N, McDannold N, Vykhodtseva N. et al . Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles.  Ultrasound Med Biol. 2004;  30 979-989
• 59 Shimamura M, Sato N, Taniyama Y. et al . Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound.  Gene Ther. 2004;  11 1532-1539
• 60 Manome Y, Nakayama N, Nakayama K. et al . Insonation facilitates plasmid DNA transfection into the central nervous system and microbubbles enhance the effect.  Ultrasound Med Biol. 2005;  31 693-702
• 61 Shimamura M, Sato N, Taniyama Y. et al . Gene transfer into adult rat spinal cord using naked plasmid DNA and ultrasound microbubbles.  J Gene Med. 2005;  7 1468-1474
• 62 Koike H, Tomita N, Azuma H. et al . An efficient gene transfer method mediated by ultrasound and microbubbles into the kidney.  J Gene Med. 2005;  7 108-116
• 63 Ng Y Y, Hou C C, Wang W. et al . Blockade of NFkappaB activation and renal inflammation by ultrasound-mediated gene transfer of Smad7 in rat remnant kidney.  Kidney Int Suppl. 2005;  S83-91
• 64 Hou C C, Wang W, Huang X R. et al . Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney.  Am J Pathol. 2005;  166 761-771
• 65 Ohta S, Suzuki K, Tachibana K. et al . Microbubble-enhanced sonoporation: efficient gene transduction technique for chick embryos.  Genesis. 2003;  37 91-101
• 66 Endoh M, Koibuchi N, Sato M. et al . Fetal gene transfer by intrauterine injection with microbubble-enhanced ultrasound.  Mol Ther. 2002;  5 501-508
• 67 Miao C H, Brayman A A, Loeb K R. et al . Ultrasound enhances gene delivery of human factor IX plasmid.  Hum Gene Ther. 2005;  16 893-905
• 68 Nakaya H, Shimizu T, Isobe K. et al . Microbubble-enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen-induced arthritis.  Arthritis Rheum. 2005;  52 2559-2566
• 69 Yang L, Shirakata Y, Tamai K. et al . Microbubble-enhanced ultrasound for gene transfer into living skin equivalents.  J Dermatol Sci. 2005;  40 105-114
• 70 Skyba D M, Price R J, Linka A Z. et al . Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue.  Circulation. 1998;  98 290-293
• 71 Ay T, Havaux X, Van Camp G. et al . Destruction of contrast microbubbles by ultrasound: effects on myocardial function, coronary perfusion pressure, and microvascular integrity.  Circulation. 2001;  104 461-466
• 72 Li P, Cao L Q, Dou C Y. et al . Impact of myocardial contrast echocardiography on vascular permeability: an in vivo dose response study of delivery mode, pressure amplitude and contrast dose.  Ultrasound Med Biol. 2003;  29 1341-1349
• 73 Li P, Armstrong W F, Miller D L. Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents.  Ultrasound Med Biol. 2004;  30 83-91
• 74 Borges A C, Walde T, Reibis R K. et al . Does contrast echocardiography with Optison induce myocardial necrosis in humans?.  J Am Soc Echocardiogr. 2002;  15 1080-1086
• 75 Chen S, Kroll M H, Shohet R V. et al . Bioeffects of myocardial contrast microbubble destruction by echocardiography.  Echocardiography. 2002;  19 495-500
• 76 Bekeredjian R, Chen S, Pan W. et al . Effects of ultrasound targeted microbubble destruction on cardiac gene expression.  Ultrasound Med Biol. 2004;  30 539-543