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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/micad/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-micad-lrg.png" alt="Cover of Molecular Imaging and Contrast Agent Database (MICAD)" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Molecular Imaging and Contrast Agent Database (MICAD) [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK23477_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK23477_dtls__"><div>Bethesda (MD): <a href="https://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>; 2004-2013.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/micad/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/micad/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/E9MAb99mTc/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/L19-Hi20Tc99m/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK23477_"><span class="title" itemprop="name"><sup>99m</sup>Tc-Anti-ED-B fibronectin L19-(Gy)<sub>3</sub>-Cys-Ala scFv antibody fragment</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>99m</sup>Tc-AP39</div><p class="contrib-group"><span itemprop="author">Kenneth T. Cheng</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK23477_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK23477_ai__"><div class="contrib half_rhythm"><span itemprop="author">Kenneth T. Cheng</span>, PhD<div class="affiliation small">
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National Center for Biotechnology Information, NLM, NIH, Bethesda, MD,
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<span class="before-email-separator"></span><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>
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||
</div></div></div><p class="small">Created: <span itemprop="datePublished">February 6, 2007</span>; Last Update: <span itemprop="dateModified">January 14, 2008</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="AP39Tc99m.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23477/table/AP39Tc99m.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__AP39Tc99m.T1_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;"><sup>99m</sup>Tc-Anti-ED-B fibronectin L19-(Gy)<sub>3</sub>-Cys-Ala scFv antibody fragment</td><td rowspan="9" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Abbreviated name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-AP39</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Synonym:</b>
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||
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-scFv L19, <sup>99m</sup>Tc-anti-ED-B FN scFv Ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
|
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<b>Agent Category:</b>
|
||
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Single-chain Antibody fragment (scFv)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
|
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<b>Target:</b>
|
||
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ED-B Fibronectin (FN)</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:top;">Antibody-antigen binding</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Method of detection:</b>
|
||
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Single-photon emission computed tomography (SPECT), gamma planar imaging</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
|
||
<b>Source of signal:</b>
|
||
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc</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></ul>
|
||
<ul class="simple-list"><li class="half_rhythm"><div>
|
||
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
|
||
</div></li></ul>
|
||
<br />
|
||
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Click on <a href="/entrez/viewer.fcgi?db=protein&val=5725426" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?db=nucleotide&val=31406" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nucleotide</a> (RefSeq), and <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=407105" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gene</a> for more information about ED-B fibronectin.</td></tr></tbody></table></div></div><div id="AP39Tc99m.Background"><h2 id="_AP39Tc99m_Background_">Background</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p><sup>99m</sup>Tc-Anti-ED-B fibronectin L19-(Gly)<sub>3</sub>-Cys-Ala scFv antibody fragment (<sup>99m</sup>Tc-AP39) is a radiolabeled molecular imaging agent developed for single-photon emission computed tomography (SPECT) imaging of tumor angiogenesis and guidance in antiangiogenic treatment (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>). <sup>99m</sup>Tc is a gamma emitter with a half-life (<i>t</i><sub>½</sub>) of 6.02 h.</p><p>Angiogenesis is a process of development and growth of new blood vessels from pre-existing vessels (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.2">2</a>). Tumor growth depends on the formation of new blood vessels via this process. Normal angiogenesis is orderly and highly regulated, whereas tumor angiogenesis is chaotic and irregular. Abnormal angiogenesis is important in the carcinogenesis, growth and progression of human solid and hematologic tumors (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.3">3</a>). Fibronectins (FNs) are a widely distributed family of universal cell-adhesion molecules (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>). FN is a polymorphic glycoprotein of ~2500 amino acids and has a high molecular mass of 250−280 kDa. FN occurs in soluble form in plasma and other body fluids and in insoluble form in the extracellular matrixes (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.4">4</a>, <a class="bk_pop" href="#AP39Tc99m.EXTYLES.5">5</a>). Both forms are dimers composed of a series of repeating units of three types and joined by two disulfide bonds at the carboxyl terminus of the molecule. FN polymorphism arises from alternative splicing patterns of the pre-mRNA or post-translational modifications of FN itself (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.5">5</a>). Alternative splicing in three different regions may generate 20 different FN subunit isoforms. The splice variant ED-B FN, which is highly expressed during angiogenesis in both neoplastic and normal tissues (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.6">6</a>), is an oncofetal antigen expressed at different levels in the stroma associated with the neovasculature of solid tumors. High levels of ED-B expression have been found in primary and metastatic tumors in breast, colorectal, and non-small cell lung cancer (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>, <a class="bk_pop" href="#AP39Tc99m.EXTYLES.7">7-9</a>).</p><p>Molecular imaging of angiogenesis offers serial non-invasive evaluation of both location and growth dynamics of tumors (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.10">10</a>) SPECT or positron emission tomography imaging with the appropriate radiolabeled tracer targeted to angiogenic pathways may allow the evaluation of specific aspects of tumor vascular biology (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.9">9</a>). A molecular probe that targets ED-B FN can be both an early tumor marker and a tool to monitor the success of antiangiogenic cancer therapy. The single-chain antibody fragment (scFv), L19, with a high affinity to ED-B FN was developed by Pini et al. (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.11">11</a>). Radioiodinated L19 showed specific accumulation around tumor neovasculature and tumor stroma with high ED-B expression (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.12">12</a>, <a class="bk_pop" href="#AP39Tc99m.EXTYLES.13">13</a>). In an effort to prepare a stable <sup>99m</sup>Tc-labeled L19, Berndorff et al. (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>) inserted the amino acid sequence (Gly)3-Cys-Ala at the C terminus of L19 to produce the recombinant protein, AP39 The authors suggested that a <sup>99m</sup>Tc(V) oxo metal complex could be formed. <sup>99m</sup>Tc-AP39 appeared to have favorable biodistribution and imaging properties in mice bearing murine embryonal teratocarcinoma (F9).</p></div><div id="AP39Tc99m.Synthesis"><h2 id="_AP39Tc99m_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29%29%20AND%20synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Pini et al. (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.11">11</a>) constructed and used a large synthetic phage display human antibody library (>3 x 10<sup>8</sup> clones) to produce L19 with a very high affinity of dissociation constant (<i>K</i><sub>d</sub>) of 54 pM to the ED-B domain of FN. L19 was cloned in scFv configuration in the novel phagemid vector, pDN332. Berndorff et al. (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>) prepared the L19 derivative by modifying the sequence of scFv LP19 to encode the <sup>99m</sup>Tc binding motif (Gly)<sub>3</sub>-Cys-Ala at the C-terminal end of the VL chain. The DNA sequence encoding this LP19 derivative was cloned into the prokaryotic expression vector pDN5 with isopropyl-1-thio-β-<span class="small-caps">d</span>-galactoside (IPTG)-inducible promoter and the ampicillin resistance marker.AP39 was isolated and purified from the soluble fraction of the French press lysate of the <i>Escherichia coli</i> culture. Before radiolabeling, AP39 was reduced by Tris-(2-carboxyethyl)phosphine hydrochloride (TCEP) in sodium phosphate (Na<sub>2</sub>HPO<sub>4</sub>) buffer (pH 7.4). The reaction mixture was gently shaken for 1 h at room temperature. TCEP was then removed by chromatography. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the purified product confirmed the transformation of the S-S-dimeric AP39 to the SH-monomeric AP39 and associative dimer form. For radiolabeling, reduced AP39 in phosphate- buffered saline was added to disodium-<span class="small-caps">l</span>-tartrate and diluted with Na<sub>2</sub>HPO<sub>4</sub> buffer. <sup>99m</sup>Tc pertechnetate and tin-II chloride (SnCl<sub>2</sub> in 0.1 mol/L hydrochloric acid) were added. The reaction mixture was shaken for 30 min at 37ºC. <sup>99m</sup>Tc-AP39 was purified by gel chromatography. The radiochemical yield was >50% after purification. The radiochemical purity was >95%. By high-performance liquid chromatography analysis, <sup>99m</sup>Tc-AP39 appeared to be a mixture of predominantly dimeric (~80%) and monomeric (~16%) <sup>99m</sup>Tc-AP39. The specific activity of <sup>99m</sup>Tc-AP39 was 35 MBq/nmol [0.95 mCi/nmol(dimer)].</p></div><div id="AP39Tc99m.In_Vitro_Studies_Tes"><h2 id="_AP39Tc99m_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29%29%20AND%20in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Berndorff et al. (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>) determined the <i>in vitro</i> immunoreactivity of <sup>99m</sup>Tc-AP39 by using affinity chromatography with ED-B FN-conjugated Sepharose. <sup>99m</sup>Tc-AP39 showed an immunoreactivity of 96%.</p></div><div id="AP39Tc99m.Animal_Studies"><h2 id="_AP39Tc99m_Animal_Studies_">Animal Studies</h2><div id="AP39Tc99m.Rodents"><h3>Rodents</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29%29%20AND%20rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Biodistribution studies (<i>n</i> = 3) of <sup>99m</sup>Tc-AP39 were performed in nude mice bearing the murine teratocarcinoma F9 (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>). F9 tumors were previously reported to express high levels of ED-B FN (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.13">13</a>). <sup>99m</sup>Tc-AP39 showed rapid blood clearance and radioactivity localization in the tumor. The radioactivity levels of <sup>99m</sup>Tc-AP39 in percentage of the injected dose per g (% ID/g) in the tumor were 5.2 ± 2.5 (0.25 h), 6.1 ± 2.0 (1 h), 8.3 ± 3.2 (3 h), 8.7 ± 52.5 (5 h), and 2.8 ± 1.4 (24 h). The tumor/blood ratios were 0.4 ± 0.2 (0.25 h), 1.6 ± 0.2 (1 h), 6.4 ± 2.9 (3 h), 9.0 ± 6.5 (5 h), and 17.2 ± 6.8 (24 h). <sup>99m</sup>Tc-AP39 appeared to be excreted primarily by the kidneys. The radioactivity levels (% ID/g) in the kidneys were 48.2 ± 4.2 (0.25 h), 21.8 ± 2.5 (1 h), 8.6 ± 0.6 (3 h), 7.9 ± 0.4 (5 h), and 2.6 ± 0.4 (24 h). About 64.5% ID was excreted <i>via</i> the urine after 24 h. There was little radioactivity accumulation in other nontarget organs. The authors suggested that the absence of radioactivity in the thyroid indicated no significant release of unlabeled <sup>99m</sup>Tc from <sup>99m</sup>Tc-AP39.</p><p>Gamma imaging was performed in mice bearing 80−100 mm<sup>2</sup> s.c.F9 tumors (<a class="bk_pop" href="#AP39Tc99m.EXTYLES.1">1</a>). Each mouse was injected with 4−7 MBq (0.11−0.19 mCi) <sup>99m</sup>Tc-AP39. Imaging with <sup>99m</sup>Tc-AP39 gave clear tumor images for at least 24 h with low background radioactivities. The kidneys were visualized at 3 and 5 h. The liver and bladder were the only other organs weakly detected at early time points.</p></div><div id="AP39Tc99m.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29%29%20AND%20%28dog%20OR%20rabbit%20OR%20pig%20OR%20sheep%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="AP39Tc99m.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29%29%20AND%20%28primate%20NOT%20human%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="AP39Tc99m.Human_Studies"><h2 id="_AP39Tc99m_Human_Studies_">Human Studies</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%28%2899mTc-AP39%29%20OR%20%28Radiolabeled%20anti-fibronectin%20antibody%29%29%20AND%20human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="AP39Tc99m.references"><h2 id="_AP39Tc99m_references_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.1">Berndorff D. , Borkowski S. , Moosmayer D. , Viti F. , Muller-Tiemann B. , Sieger S. , Friebe M. , Hilger C.S. , Zardi L. , Neri D. , Dinkelborg L.M. Imaging of tumor angiogenesis using 99mTc-labeled human recombinant anti-ED-B fibronectin antibody fragments. <span><span class="ref-journal">J Nucl Med. </span>2006;<span class="ref-vol">
|
||
<strong>47</strong>
|
||
</span>(10):1707–16.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17015908" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17015908</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.2">Shinkaruk S. , Bayle M. , Lain G. , Deleris G. Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy. <span><span class="ref-journal">Curr Med Chem Anticancer Agents. </span>2003;<span class="ref-vol">
|
||
<strong>3</strong>
|
||
</span>(2):95–117.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12678905" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12678905</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.3">Ranieri G. , Patruno R. , Ruggieri E. , Montemurro S. , Valerio P. , Ribatti D. Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. <span><span class="ref-journal">Curr Med Chem. </span>2006;<span class="ref-vol">
|
||
<strong>13</strong>
|
||
</span>(16):1845–57.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16842197" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16842197</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.4">Carnemolla B. , Balza E. , Siri A. , Zardi L. , Nicotra M.R. , Bigotti A. , Natali P.G. A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precursors. <span><span class="ref-journal">J Cell Biol. </span>1989;<span class="ref-vol">
|
||
<strong>108</strong>
|
||
</span>(3):1139–48.</span> [<a href="/pmc/articles/PMC2115391/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2115391</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/2646306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2646306</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.5">Kosmehl H. , Berndt A. , Katenkamp D. Molecular variants of fibronectin and laminin: structure, physiological occurrence and histopathological aspects. <span><span class="ref-journal">Virchows Arch. </span>1996;<span class="ref-vol">
|
||
<strong>429</strong>
|
||
</span>(6):311–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8982375" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8982375</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.6">Castellani P. , Viale G. , Dorcaratto A. , Nicolo G. , Kaczmarek J. , Querze G. , Zardi L. The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis. <span><span class="ref-journal">Int J Cancer. </span>1994;<span class="ref-vol">
|
||
<strong>59</strong>
|
||
</span>(5):612–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7525495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7525495</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.7">Kaczmarek J. , Castellani P. , Nicolo G. , Spina B. , Allemanni G. , Zardi L. Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues. <span><span class="ref-journal">Int J Cancer. </span>1994;<span class="ref-vol">
|
||
<strong>59</strong>
|
||
</span>(1):11–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7927891" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7927891</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.8">Pujuguet P. , Hammann A. , Moutet M. , Samuel J.L. , Martin F. , Martin M. Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts. <span><span class="ref-journal">Am J Pathol. </span>1996;<span class="ref-vol">
|
||
<strong>148</strong>
|
||
</span>(2):579–92.</span> [<a href="/pmc/articles/PMC1861682/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1861682</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8579120" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8579120</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.9">Santimaria M. , Moscatelli G. , Viale G.L. , Giovannoni L. , Neri G. , Viti F. , Leprini A. , Borsi L. , Castellani P. , Zardi L. , Neri D. , Riva P. Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. <span><span class="ref-journal">Clin Cancer Res. </span>2003;<span class="ref-vol">
|
||
<strong>9</strong>
|
||
</span>(2):571–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12576420" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12576420</span></a>]</div></dd><li><div class="bk_ref" id="AP39Tc99m.EXTYLES.10">10. Laking, G.R. and P.M. Price, Positron emission tomographic imaging of angiogenesis and vascular function. Br J Radiol, 2003. 76 Spec No 1: p. S50-9. [<a href="https://pubmed.ncbi.nlm.nih.gov/15456714" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15456714</span></a>]</div></li><dt>11.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.11">Pini A. , Viti F. , Santucci A. , Carnemolla B. , Zardi L. , Neri P. , Neri D. Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel. <span><span class="ref-journal">J Biol Chem. </span>1998;<span class="ref-vol">
|
||
<strong>273</strong>
|
||
</span>(34):21769–76.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9705314" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9705314</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.12">Tarli L. , Balza E. , Viti F. , Borsi L. , Castellani P. , Berndorff D. , Dinkelborg L. , Neri D. , Zardi L. A high-affinity human antibody that targets tumoral blood vessels. <span><span class="ref-journal">Blood. </span>1999;<span class="ref-vol">
|
||
<strong>94</strong>
|
||
</span>(1):192–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10381513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10381513</span></a>]</div></dd><dt>13.</dt><dd><div class="bk_ref" id="AP39Tc99m.EXTYLES.13">Borsi L. , Balza E. , Bestagno M. , Castellani P. , Carnemolla B. , Biro A. , Leprini A. , Sepulveda J. , Burrone O. , Neri D. , Zardi L. Selective targeting of tumoral vasculature: comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin. <span><span class="ref-journal">Int J Cancer. </span>2002;<span class="ref-vol">
|
||
<strong>102</strong>
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</span>(1):75–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12353237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12353237</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK23477</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/20641676" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">20641676</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/micad/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/E9MAb99mTc/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/L19-Hi20Tc99m/" title="Next page in this title">Next ></a></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK23477/?report=reader">PubReader</a></li><li><a href="/books/NBK23477/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK23477" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK23477" style="display:none" title="Cite this Page"><div class="bk_tt">Cheng KT. 99mTc-Anti-ED-B fibronectin L19-(Gy)3-Cys-Ala scFv antibody fragment. 2007 Feb 6 [Updated 2008 Jan 14]. 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></div></div></li><li><a href="/books/NBK23477/pdf/Bookshelf_NBK23477.pdf">PDF version of this page</a> (136K)</li><li><a href="/books/n/micad/toc/bin/micad.csv">MICAD summary (CSV file)</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#AP39Tc99m.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#AP39Tc99m.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#AP39Tc99m.In_Vitro_Studies_Tes" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#AP39Tc99m.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#AP39Tc99m.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#AP39Tc99m.references" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Search MICAD</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-application" id="Shutter"></a></div><div class="portlet_content"><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmSearch" method="get" action="/books/NBK5330/" id="frmSearch"><script type="text/javascript" src="/corehtml/pmc//js/bookshelf/micad.js">/**/</script><label class="offscreen_noflow" for="txtfield">Search term</label><input id="txtfield" type="text" name="f1_term" size="22" onKeyPress="KeyPress('micad',event,'/books/NBK5330/','')" /><button name="f1_search" type="submit">Go</button><button onclick="this.form.reset();" type="reset">Clear</button><p><b>Limit my Search:</b></p><div class="clearfix"><label for="detection">Method of detection:</label><div class="right"><select name="detection" id="detection" style="width:200px"><option value="" selected="selected">Any</option><option value="(MRI OR "Magnetic resonance imaging" OR MRS)">MRI</option><option value="Multimodal">Multimodal imaging</option><option value="Optical">Optical imaging</option><option value="PET">PET</option><option value="Photoacoustic">Photoacoustic imaging</option><option value="(SPECT OR planar)">SPECT</option><option value="Ultrasound">Ultrasound</option><option value="(x-ray OR ct)">X-ray, CT</option></select></div></div><div class="clearfix"><label for="signal">Source of signal/contrast:</label><div class="right"><select name="signal" id="signal" style="width:200px"><option value="" selected="selected">Any</option><optgroup label="MRI agents"><option value="(Copper OR Cu)">Copper</option><option value="(Europium OR Eu3+)">Europium</option><option value="(Fluorine OR 19F)">Fluorine</option><option value="(Gadolinium OR Gd3+)">Gadolinium</option><option value=""Hyperpolarized 13C"">Hyperpolarized 13C</option><option value=""Iron oxide"">Iron oxide</option><option value=""Nitroxide radicals"">Nitroxide radicals</option><option value="(Oxygen OR 17O)">Oxygen</option><option value="Thulium">Thulium</option></optgroup><optgroup label="Multimodal agents"><option value="((Gadolinium OR Gd3+) AND Optical)">Gadolinium and optical</option><option value="((Gadolinium OR Gd3+) AND (Gold OR Au))">Gadolinium and Gold</option><option value="("Iron oxide" AND (64Cu OR 124I OR 111In))">Iron oxide and
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value="Nanobubbles">Nanobubbles</option></optgroup><optgroup label="X-ray and CT agents"><option value="(Bismuth OR Bi)">Bismuth</option><option value="(Gold OR Au)">Gold</option><option value="Iodine">Iodine</option></optgroup></select></div></div><div class="clearfix"><label for="agent">Agent Category:</label><div class="right"><select name="agent" id="agent" style="width:200px"><option value="" selected="selected">Any</option><option value="(antibody OR trastuzumab OR immunoglobulin)">Antibodies</option><option value="(bacteria OR bacteriophage OR coli)">Bacteria</option><option value="cell">Cells</option><option value="(compound OR "amino acid" OR "folic acid" OR "cage molecule" OR carbohydrate OR copolymers OR polymer OR "small molecule" OR macromolecule OR triiodobenzoate OR estradiol OR glycosaminoglycan)">Compounds</option><option value="ligand">Ligands</option><option value="(lipid OR liposome OR liposomes">Lipids</option><option value="metal">Metal</option><option value="(nanoparticle OR nanoparticles OR nanotubes OR "iron oxide")">Nanoparticles</option><option value="(siRNA OR "nucleic acid" OR oligonucleotide)">Nucleic acids</option><option value="peptide">Peptides</option><option value="polyeptide">Polyeptides</option><option value="(protein OR albumin OR chemokin OR immunoprotein OR luciferase OR albumin)">Proteins</option><option value="(virus OR adenovirus)">Viruses</option></select></div></div><div class="clearfix"><label for="target">Target Category:</label><div class="right"><select name="target" id="target" style="width:200px"><option value="" selected="selected">Any</option><option value="acceptor">Acceptors</option><option value=""adhesion molecule"">Adhesion molecules</option><option value="(antigen OR antibody-antigen)">Antigens</option><option value="(enzyme OR enzymes OR enzyme-substrate)">Enzymes</option><option value="(lipids OR lipophilic cation)">Lipids</option><option value="(receptor OR receptors OR receptor-ligand OR 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