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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Microbubbles conjugated with single-chain Cys-tagged vascular endothelial growth factor-121 - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="citation_author" content="Kam Leung">
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<meta name="og:description" content="Ultrasound is the most widely used imaging modality (1) and its role in noninvasive molecular imaging is expanding with ligand-carrying microbubbles (MBs) (2). MBs are composed of spherical cavities filled by a gas encapsulated in a shell. The shells are made of phospholipids, surfactant, denatured human serum albumin, or synthetic polymer. Ligands and antibodies can be incorporated into the shell surface of MBs. MBs are usually 1&ndash;8 &mu;m in diameter, and they provide a strongly reflective interface and resonate to ultrasound waves. MBs are used as ultrasound contrast agents in imaging of inflammation, angiogenesis, intravascular thrombus, and tumors (3-5). They also have the potential to be used for drug and gene delivery (6).">
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false" itemprop="text"><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figscVEGFMBTncchemicalnamemicrobubbles"><a href="/books/NBK52896/table/scVEGF-MB.T.nc_chemical_namemicrobubbles/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobscVEGFMBTncchemicalnamemicrobubbles"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="scVEGF-MB.T.nc_chemical_namemicrobubbles"><a href="/books/NBK52896/table/scVEGF-MB.T.nc_chemical_namemicrobubbles/?report=objectonly" target="object" rid-ob="figobscVEGFMBTncchemicalnamemicrobubbles">Table</a></h4><p class="float-caption no_bottom_margin">
<i>In vitro</i>
Rodents
</p></div></div><div id="scVEGF-MB.Background"><h2 id="_scVEGF-MB_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=scVEGF%20MB" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Ultrasound is the most widely used imaging modality (<a class="bibr" href="#scVEGF-MB.REF.1" rid="scVEGF-MB.REF.1">1</a>) and its role in noninvasive molecular imaging is expanding with ligand-carrying microbubbles (MBs) (<a class="bibr" href="#scVEGF-MB.REF.2" rid="scVEGF-MB.REF.2">2</a>). MBs are composed of spherical cavities filled by a gas encapsulated in a shell. The shells are made of phospholipids, surfactant, denatured human serum albumin, or synthetic polymer. Ligands and antibodies can be incorporated into the shell surface of MBs. MBs are usually 1&#x02013;8 &#x003bc;m in diameter, and they provide a strongly reflective interface and resonate to ultrasound waves. MBs are used as ultrasound contrast agents in imaging of inflammation, angiogenesis, intravascular thrombus, and tumors (<a class="bibr" href="#scVEGF-MB.REF.3" rid="scVEGF-MB.REF.3 scVEGF-MB.REF.4 scVEGF-MB.REF.5">3-5</a>). They also have the potential to be used for drug and gene delivery (<a class="bibr" href="#scVEGF-MB.REF.6" rid="scVEGF-MB.REF.6">6</a>).</p><p>Vascular endothelial growth factor (VEGF) consists of at least six isoforms with various numbers of amino acids (121, 145, 165, 183, 189, and 206 amino acids) produced through alternative splicing (<a class="bibr" href="#scVEGF-MB.REF.7" rid="scVEGF-MB.REF.7">7</a>). VEGF<sub>121</sub>, VEGF<sub>165</sub>, and VEGF<sub>189</sub> are the forms secreted by most cell types, and they are active as homodimers linked by disulfide bonds. VEGF<sub>121</sub> does not bind to heparin like the other VEGF species (<a class="bibr" href="#scVEGF-MB.REF.8" rid="scVEGF-MB.REF.8">8</a>). VEGF is a potent angiogenic factor that induces proliferation, sprouting, migration, and tube formation of endothelial cells. There are three high-affinity tyrosine kinase VEGF receptors (VEGFRs) on endothelial cells (VEGFR-1, Flt-1; VEGFR-2, KDR/Flt-1; and VEGFR-3, Flt-4). Several types of non-endothelial cells, such as hematopoietic stem cells, melanoma cells, monocytes, osteoblasts, and pancreatic &#x003b2; cells, also express VEGFRs (<a class="bibr" href="#scVEGF-MB.REF.7" rid="scVEGF-MB.REF.7">7</a>).</p><p>VEGFRs have been found to be overexpressed in various tumor cells and tumor-associated endothelial cells but are not detectable in quiescent endothelial cells (<a class="bibr" href="#scVEGF-MB.REF.9" rid="scVEGF-MB.REF.9">9</a>). Inhibition of VEGFR function has been shown to inhibit pathological angiogenesis as well as tumor growth and metastasis (<a class="bibr" href="#scVEGF-MB.REF.10" rid="scVEGF-MB.REF.10 scVEGF-MB.REF.11">10, 11</a>). Radiolabeled VEGF has been developed as a tracer for imaging solid tumors and angiogenesis in humans (<a class="bibr" href="#scVEGF-MB.REF.12" rid="scVEGF-MB.REF.12 scVEGF-MB.REF.13 scVEGF-MB.REF.14">12-14</a>). MBs conjugated to either peptides or antibodies against integrins, cell adhesion molecules, and VEGFRs have previously been studied for the non-invasive assessment and imaging of tumor angiogenesis (<a class="bibr" href="#scVEGF-MB.REF.15" rid="scVEGF-MB.REF.15 scVEGF-MB.REF.16 scVEGF-MB.REF.17 scVEGF-MB.REF.18">15-18</a>). A 15-amino-acid long fusion tag (Cys-tag) was developed for site-specific conjugation <i>via</i> the free sulfhydryl group of Cys. Backer et al. (<a class="bibr" href="#scVEGF-MB.REF.19" rid="scVEGF-MB.REF.19">19</a>) prepared a Cys-tagged vector of VEGF<sub>121</sub> by cloning two single-chain 3&#x02013;112 amino acid fragments of VEGF<sub>121</sub> joining head-to-tail to express as scVEGF, which binds to VEGFR-2. In this chapter, Anderson et al. (<a class="bibr" href="#scVEGF-MB.REF.20" rid="scVEGF-MB.REF.20">20</a>) studied ultrasonic imaging of tumor vasculature using MBs conjugated with scVEGF (scVEGF-MBs) in mice bearing human tumor xenografts.</p><div id="scVEGF-MB.Related_Resource_Links"><h3>Related Resource Links:</h3><ul><li class="half_rhythm"><div>Chapters in MICAD (<a href="/sites/entrez?Db=books&#x00026;Cmd=DetailsSearch&#x00026;Term=VEGFR+AND+micad%5Bbook%5D" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">VEGFR</a>)</div></li><li class="half_rhythm"><div>Gene information in NCBI (<a href="/sites/entrez?Db=gene&#x00026;Cmd=DetailsSearch&#x00026;Term=3791" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">VEGFR</a>)</div></li><li class="half_rhythm"><div>Articles in Online Mendelian Inheritance in Man (OMIM) (<a href="/sites/entrez?Db=omim&#x00026;Cmd=DetailsSearch&#x00026;Term=VEGFR" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">VEGFR</a>)</div></li><li class="half_rhythm"><div>Clinical trials (<a href="http://www.clinicaltrials.gov/ct2/results?term=VEGFR" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">VEGFR</a>)</div></li><li class="half_rhythm"><div>FDA Drug information (<a href="http://google2.fda.gov/search?q=VEGFR&#x00026;client=FDAgov&#x00026;site=FDAgov&#x00026;lr=&#x00026;proxystylesheet=FDAgov&#x00026;output=xml_no_dtd&#x00026;getfields=*&#x00026;x=12&#x00026;y=7" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">VEGFR</a>)</div></li></ul></div></div><div id="scVEGF-MB.Synthesis"><h2 id="_scVEGF-MB_Synthesis_">Synthesis</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=scVEGF%20MB+synthesis" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Backer et al. (<a class="bibr" href="#scVEGF-MB.REF.19" rid="scVEGF-MB.REF.19">19</a>) reported the synthesis of a Cys-tagged vector of VEGF<sub>121</sub> by cloning two single-chain 3&#x02013;112 amino acid fragments of VEGF<sub>121</sub> joining head-to-tail to express as scVEGF in <i>Escherichia coli</i> for mammalian cell production. Maleimide-bearing MBs (maleimide-MB) were reacted with a thio-containing scVEGF construct for 2 h at room temperature (<a class="bibr" href="#scVEGF-MB.REF.20" rid="scVEGF-MB.REF.20">20</a>). scVEGF-MBs had a mean diameter of 2.5 &#x000b1; 1.0 &#x000b5;m. There were 1.2 &#x000d7; 10<sup>5</sup> scVEGF molecules per MB.</p></div><div id="scVEGF-MB.In_Vitro_Studies_Testing_in_Ce"><h2 id="_scVEGF-MB_In_Vitro_Studies_Testing_in_Ce_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=scVEGF%20MB+in+vitro+studies" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Anderson et al. (<a class="bibr" href="#scVEGF-MB.REF.20" rid="scVEGF-MB.REF.20">20</a>) reported that scVEGF-MBs or maleimide-MBs (5 &#x000d7; 10<sup>6</sup>/ml) perfused for 5 min through flow chambers coated with VEGFR-2&#x02013;positive porcine aortic endothelial cells at a wall shear rate of 1.0 dyne/cm<sup>2</sup>. There was a significantly (<i>P</i> &#x0003c; 0.01) greater number of scVEGF-MBs attached to the endothelial cells (25 &#x000b1; 4 MBs/cell) than maleimide-MBs (5 &#x000b1; 1 MBs/cell). <i>In vitro</i> ultrasound studies were performed using flow assay with agar phantom, which was immobilized with murine VEGFR-2 or control casein. The mean pixel amplitude of adherent scVEGF-MBs (1 &#x000d7; 10<sup>6</sup>/ml) was significantly higher (<i>P</i> &#x0003c; 0.01) in VEGFR-2&#x02013;coated phantom (7 &#x000b1; 2 dB) than in casein-coated phantom (0.2 dB).</p></div><div id="scVEGF-MB.Animal_Studies"><h2 id="_scVEGF-MB_Animal_Studies_">Animal Studies</h2><div id="scVEGF-MB.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=scVEGF%20MB+rodentia" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Anderson et al. (<a class="bibr" href="#scVEGF-MB.REF.20" rid="scVEGF-MB.REF.20">20</a>) performed an ultrasound assessment of MB binding in mice bearing murine MC-38 colon adenocarcinoma tumors. Ultrasound was performed at 6 min after injection of scVEGF-MBs or maleimide-MBs (2 &#x000d7; 10<sup>7</sup>/mouse). The mean pixel amplitudes in the tumor were 8.46 &#x000b1; 1.61 dB and 1.58 &#x000b1; 0.83 dB for scVEGF-MBs and maleimide-MBs, respectively. The contrast enhancement of scVEGF-MBs to the tumors was significantly higher than that of maleimide-MBs (<i>P</i> &#x0003c; 0.01). The tumor contrast induced by scVEGF-MBs returned to background level (~1 dB) when a high M1, destructive acoustic pulse was administered to the tumor tissues. However, no blocking studies were performed.</p></div><div id="scVEGF-MB.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=scVEGF%20MB%20and%20%28dog%20or%20pig%20or%20sheep%20or%20rabbit%29" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="scVEGF-MB.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=scVEGF%20MB+Non+Human+Primates" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div></div><div id="scVEGF-MB.Human_Studies"><h2 id="_scVEGF-MB_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=scVEGF%20MB+Human+Studies" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="scVEGF-MB.NIH_Support"><h2 id="_scVEGF-MB_NIH_Support_">NIH Support</h2><p>1R43 EB007857, 2R44 EB007857, 2R44 CA113080</p></div><div id="scVEGF-MB.References"><h2 id="_scVEGF-MB_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.1">Wells P.N.
<em>Physics and engineering: milestones in medicine.</em>
<span><span class="ref-journal">Med Eng Phys. </span>2001;<span class="ref-vol">23</span>(3):147&ndash;53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11410379" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11410379</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.2">Liang H.D., Blomley M.J.
<em>The role of ultrasound in molecular imaging.</em>
<span><span class="ref-journal">Br J Radiol. </span>2003;<span class="ref-vol">76</span>(Spec No 2):S140&ndash;50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15572336" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15572336</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.3">Klibanov A.L.
<em>Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging.</em>
<span><span class="ref-journal">Bioconjug Chem. </span>2005;<span class="ref-vol">16</span>(1):9&ndash;17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15656569" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15656569</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.4">Lindner J.R.
<em>Microbubbles in medical imaging: current applications and future directions.</em>
<span><span class="ref-journal">Nat Rev Drug Discov. </span>2004;<span class="ref-vol">3</span>(6):527&ndash;32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15173842" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15173842</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.5">Villanueva F.S., Wagner W.R., Vannan M.A., Narula J.
<em>Targeted ultrasound imaging using microbubbles.</em>
<span><span class="ref-journal">Cardiol Clin. </span>2004;<span class="ref-vol">22</span>(2):283&ndash;98.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15158940" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15158940</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.6">Dijkmans P.A., Juffermans L.J., Musters R.J., van Wamel A., ten Cate F.J., van Gilst W., Visser C.A., de Jong N., Kamp O.
<em>Microbubbles and ultrasound: from diagnosis to therapy.</em>
<span><span class="ref-journal">Eur J Echocardiogr. </span>2004;<span class="ref-vol">5</span>(4):245&ndash;56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15219539" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15219539</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.7">Ferrara N.
<em>Vascular endothelial growth factor: basic science and clinical progress.</em>
<span><span class="ref-journal">Endocr Rev. </span>2004;<span class="ref-vol">25</span>(4):581&ndash;611.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15294883" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15294883</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.8">Cohen T., Gitay-Goren H., Sharon R., Shibuya M., Halaban R., Levi B.Z., Neufeld G.
<em>VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells.</em>
<span><span class="ref-journal">J Biol Chem. </span>1995;<span class="ref-vol">270</span>(19):11322&ndash;6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7744769" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 7744769</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.9">Itakura J., Ishiwata T., Shen B., Kornmann M., Korc M.
<em>Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer.</em>
<span><span class="ref-journal">Int J Cancer. </span>2000;<span class="ref-vol">85</span>(1):27&ndash;34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10585578" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 10585578</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.10">Ferrara N.
<em>Vascular endothelial growth factor as a target for anticancer therapy.</em>
<span><span class="ref-journal">Oncologist. </span>2004;<span class="ref-vol">9</span> Suppl 1:2&ndash;10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15178810" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15178810</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.11">Hicklin D.J., Ellis L.M.
<em>Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis.</em>
<span><span class="ref-journal">J Clin Oncol. </span>2005;<span class="ref-vol">23</span>(5):1011&ndash;27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15585754" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15585754</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.12">Li S., Peck-Radosavljevic M., Koller E., Koller F., Kaserer K., Kreil A., Kapiotis S., Hamwi A., Weich H.A., Valent P., Angelberger P., Dudczak R., Virgolini I.
<em>Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy.</em>
<span><span class="ref-journal">Int J Cancer. </span>2001;<span class="ref-vol">91</span>(6):789&ndash;96.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11275981" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11275981</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.13">Li S., Peck-Radosavljevic M., Kienast O., Preitfellner J., Hamilton G., Kurtaran A., Pirich C., Angelberger P., Dudczak R.
<em>Imaging gastrointestinal tumours using vascular endothelial growth factor-165 (VEGF165) receptor scintigraphy.</em>
<span><span class="ref-journal">Ann Oncol. </span>2003;<span class="ref-vol">14</span>(8):1274&ndash;7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12881392" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12881392</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.14">Li S., Peck-Radosavljevic M., Kienast O., Preitfellner J., Havlik E., Schima W., Traub-Weidinger T., Graf S., Beheshti M., Schmid M., Angelberger P., Dudczak R.
<em>Iodine-123-vascular endothelial growth factor-165 (123I-VEGF165). Biodistribution, safety and radiation dosimetry in patients with pancreatic carcinoma.</em>
<span><span class="ref-journal">Q J Nucl Med Mol Imaging. </span>2004;<span class="ref-vol">48</span>(3):198&ndash;206.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15499293" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15499293</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.15">Villanueva F.S., Jankowski R.J., Klibanov S., Pina M.L., Alber S.M., Watkins S.C., Brandenburger G.H., Wagner W.R.
<em>Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells.</em>
<span><span class="ref-journal">Circulation. </span>1998;<span class="ref-vol">98</span>(1):1&ndash;5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9665051" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 9665051</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.16">Weller G.E., Lu E., Csikari M.M., Klibanov A.L., Fischer D., Wagner W.R., Villanueva F.S.
<em>Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1.</em>
<span><span class="ref-journal">Circulation. </span>2003;<span class="ref-vol">108</span>(2):218&ndash;24.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12835214" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12835214</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.17">Weller G.E., Villanueva F.S., Klibanov A.L., Wagner W.R.
<em>Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium.</em>
<span><span class="ref-journal">Ann Biomed Eng. </span>2002;<span class="ref-vol">30</span>(8):1012&ndash;9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12449762" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12449762</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.18">Reinhardt M., Hauff P., Linker R.A., Briel A., Gold R., Rieckmann P., Becker G., Toyka K.V., Maurer M., Schirner M.
<em>Ultrasound derived imaging and quantification of cell adhesion molecules in experimental autoimmune encephalomyelitis (EAE) by Sensitive Particle Acoustic Quantification (SPAQ).</em>
<span><span class="ref-journal">Neuroimage. </span>2005;<span class="ref-vol">27</span>(2):267&ndash;78.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15905104" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15905104</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.19">Backer M.V., Patel V., Jehning B.T., Claffey K.P., Backer J.M.
<em>Surface immobilization of active vascular endothelial growth factor via a cysteine-containing tag.</em>
<span><span class="ref-journal">Biomaterials. </span>2006;<span class="ref-vol">27</span>(31):5452&ndash;8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16843524" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 16843524</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="scVEGF-MB.REF.20">Anderson C.R., Rychak J.J., Backer M., Backer J., Ley K., Klibanov A.L.
<em>scVEGF microbubble ultrasound contrast agents: a novel probe for ultrasound molecular imaging of tumor angiogenesis.</em>
<span><span class="ref-journal">Invest Radiol. </span>2010;<span class="ref-vol">45</span>(10):579&ndash;85.</span> [<a href="/pmc/articles/PMC3426362/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC3426362</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20733505" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 20733505</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK52896_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Kam Leung</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, NIH, Bethesda, MD<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@dacim" class="oemail">vog.hin.mln.ibcn@dacim</a></div></div><div class="small">Corresponding author.</div></div><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">December 15, 2010</span>; Last Update: <span itemprop="dateModified">February 24, 2011</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&amp;targetsite=external&amp;targetcat=link&amp;targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Leung K. Microbubbles conjugated with single-chain Cys-tagged vascular endothelial growth factor-121. 2010 Dec 15 [Updated 2011 Feb 24]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/micad/Knottin-MB/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/micad/Echistatin-mb/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobscVEGFMBTncchemicalnamemicrobubbles"><div id="scVEGF-MB.T.nc_chemical_namemicrobubbles" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK52896/table/scVEGF-MB.T.nc_chemical_namemicrobubbles/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__scVEGF-MB.T.nc_chemical_namemicrobubbles_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Chemical name:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Microbubbles conjugated with single-chain Cys-tagged vascular endothelial growth factor-121</td><td rowspan="9" colspan="1" style="text-align:center;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Abbreviated name:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">scVEGF-MBs</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Synonym:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Agent Category:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polypeptide</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Target:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vascular endothelial growth factor receptor-2 (VEGFR-2)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Target Category:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Receptor</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Method of detection:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrasound</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Source of signal / contrast:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Microbubbles (MBs)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Activation:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Studies:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
<ul class="simple-list"><li class="half_rhythm"><div>
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" />
<i>In vitro</i>
</div></li><li class="half_rhythm"><div>
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
</div></li></ul>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Click on <a href="/entrez/viewer.fcgi?db=protein&#x00026;val=71051581" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?val=NM_001025368.1" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">nucleotide</a> (RefSeq), and <a href="/entrez/query.fcgi?db=gene&#x00026;cmd=Retrieve&#x00026;dopt=Graphics&#x00026;list_uids=7422" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">gene</a> for more information about VEGF.</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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