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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>[111In]-Ethylenedicysteine-murine anti-phosphotyrosine antibody - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="Molecular Imaging and Contrast Agent Database (MICAD) [Internet]">
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<meta name="citation_title" content="[111In]-Ethylenedicysteine-murine anti-phosphotyrosine antibody">
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<meta name="citation_date" content="2009/04/06">
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<meta name="citation_author" content="Arvind Chopra">
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<meta name="DC.Title" content="[111In]-Ethylenedicysteine-murine anti-phosphotyrosine antibody">
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<meta name="description" content="The overexpression or constitutive activation of non-receptor tyrosine kinase (TK) such as Src- and Bcr-Abl is one of the several mechanisms known to initiate and participate in the progression and metastasis of cancer (1, 2). Because of their role in the development of different neoplasms, small-molecule drugs such as imatinib, dasatinib, and others that block TK activity by inhibiting ATP binding to the enzyme are often used to treat patients suffering from this disease (3, 4). Because several different TK blockers are either under development or are being evaluated in clinical trials to treat cancers, it is important to be able to screen patients to determine which TK inhibitor is likely to result in a good prognosis for an individual (5). Although invasive procedures such as biopsies are routinely used to determine the efficacy of an anti-cancer treatment, a noninvasive technique such as imaging would probably be preferred to evaluate drug activity during early stages of the treatment.">
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<meta name="og:description" content="The overexpression or constitutive activation of non-receptor tyrosine kinase (TK) such as Src- and Bcr-Abl is one of the several mechanisms known to initiate and participate in the progression and metastasis of cancer (1, 2). Because of their role in the development of different neoplasms, small-molecule drugs such as imatinib, dasatinib, and others that block TK activity by inhibiting ATP binding to the enzyme are often used to treat patients suffering from this disease (3, 4). Because several different TK blockers are either under development or are being evaluated in clinical trials to treat cancers, it is important to be able to screen patients to determine which TK inhibitor is likely to result in a good prognosis for an individual (5). Although invasive procedures such as biopsies are routinely used to determine the efficacy of an anti-cancer treatment, a noninvasive technique such as imaging would probably be preferred to evaluate drug activity during early stages of the treatment.">
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id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK22989_"><span class="title" itemprop="name">[<sup>111</sup>In]-Ethylenedicysteine-murine anti-phosphotyrosine antibody</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>111</sup>In-EC-APT</div><p class="contribs">Chopra A.</p><p class="fm-aai"><a href="#_NBK22989_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figECAPT111InT1"><a href="/books/NBK22989/table/ECAPT111In.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobECAPT111InT1"><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="ECAPT111In.T1"><a href="/books/NBK22989/table/ECAPT111In.T1/?report=objectonly" target="object" rid-ob="figobECAPT111InT1">Table</a></h4><p class="float-caption no_bottom_margin">
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Rodents
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</p></div></div><div id="ECAPT111In.Background"><h2 id="_ECAPT111In_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Bcr+Abl+tyrosine+kinase" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The overexpression or constitutive activation of non-receptor tyrosine kinase (TK) such as Src- and Bcr-Abl is one of the several mechanisms known to initiate and participate in the progression and metastasis of cancer (<a class="bibr" href="#ECAPT111In.REF.1" rid="ECAPT111In.REF.1 ECAPT111In.REF.2">1, 2</a>). Because of their role in the development of different neoplasms, small-molecule drugs such as imatinib, dasatinib, and others that block TK activity by inhibiting ATP binding to the enzyme are often used to treat patients suffering from this disease (<a class="bibr" href="#ECAPT111In.REF.3" rid="ECAPT111In.REF.3 ECAPT111In.REF.4">3, 4</a>). Because several different TK blockers are either under development or are being evaluated in <a href="http://clinicaltrials.gov/ct2/results?term=tyrosine+kinase+inhibitors" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">clinical trials</a> to treat cancers, it is important to be able to screen patients to determine which TK inhibitor is likely to result in a good prognosis for an individual (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>). Although invasive procedures such as biopsies are routinely used to determine the efficacy of an anti-cancer treatment, a noninvasive technique such as imaging would probably be preferred to evaluate drug activity during early stages of the treatment.</p><p>Wu et al. envisioned that antibodies labeled with a radionuclide and directed toward an intracellular non-receptor TK could be used for the noninvasive determination of drug efficacy (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>). The investigators evaluated an ethylenedicysteine (EC)-murine anti-phosphotyrosine (APT) antibody labeled with radioactive indium (<sup>111</sup>In) (<sup>111</sup>In-EC-APT) to image the Bcr-Abl TK, which is known to be upregulated and to promote chronic myeloid leukemia (<a class="bibr" href="#ECAPT111In.REF.6" rid="ECAPT111In.REF.6">6</a>), in a mouse xenograft tumor model. The radiolabeled antibody (Ab) was also used to investigate tumor imaging changes in the animals after treatment with imatinib.</p></div><div id="ECAPT111In.Synthesis"><h2 id="_ECAPT111In_Synthesis_">Synthesis</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=labeled+Bcr+Abl+anti+tyrosine+kinase+antibody+synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The synthesis of <sup>111</sup>In-EC-APT was described in detail by Wu et al. (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>). The various biological reagents used for the studies and described in this chapter, including the control (anti-phospho-Bcr-Abl Ab) and the murine APT 4G10 Abs, were obtained from commercial sources. EC was conjugated to the APT Ab, murine immunoglobulin G<sub>1</sub> (IgG<sub>1</sub>), anti-phospho-Bcr-Abl Ab, and bovine serum albumin (BSA) with sulfo-<i>N</i>-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as the coupling agents.</p><p>For the conjugation of EC, the various bioreagents were respectively incubated with a mixture of EC, NHS, and EDC for 17 h at room temperature. The purification and final percent yield of the respective EC-conjugated bioreagents and the ratio of chelating agent per antibody molecule were not reported. For labeling with <sup>111</sup>In, the radionuclide was mixed with the respective EC-conjugated bioreagent to obtain <sup>111</sup>In-EC-BSA, <sup>111</sup>In-EC-IgG<sub>1</sub>, <sup>111</sup>In-EC-Bcr-Abl, and <sup>111</sup>In-EC-APT. Purification of the radiolabeled bioreagents was not reported. Radiochemical purity of the <sup>111</sup>In-labeled biochemicals was reported to be >95%, as determined with thin-layer chromatography. The specific activity and stability of the various labeled bioreagents were not reported.</p></div><div id="ECAPT111In.In_Vitro_Studies_Tes"><h2 id="_ECAPT111In_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=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="ECAPT111In.Animal_Studies"><h2 id="_ECAPT111In_Animal_Studies_">Animal Studies</h2><div id="ECAPT111In.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=111In+EC+APT+Rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Tumor imaging studies were performed with immunodeficient mice bearing K562 cell tumors, a human chronic myeloid leukemia cell line that constitutively expresses activated Bcr-Abl TK (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>). The mice were divided into five groups, each consisting of five animals. The first group received <sup>111</sup>In-EC-BSA to visualize normal blood flow in the tumor; the second group received <sup>111</sup>In-EC-APT to determine tumor specificity of the labeled Ab, and the third group was treated with imatinib for 3 days before the <sup>111</sup>In-EC-APT injection and during the imaging study (a total of 4 or 5 d). Two other groups of animals received either <sup>111</sup>In-EC-IgG<sub>1</sub> or <sup>111</sup>In-EC-Bcr-Abl to serve as the negative and positive controls, respectively. Images were acquired at various time points up to 48 h after the radiobiochemical injection.</p><p>Determination of the tumor/non-tumor count densities after planar scintigraphy revealed that there was an increased uptake of <sup>111</sup>In-EC-APT by the tumors compared with <sup>111</sup>In-EC-BSA (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>). Mice treated with imatinib showed a reduced (<i>P</i> < 0.05) <sup>111</sup>In-EC-APT uptake. At 48 h after treatment with the radiotracers, one animal from each group was subjected to single-photon emission computed tomography-computed tomography (SPECT-CT), which produces a dynamic image (for details see Wu et al. (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>)) of the combined functional and structural features of the tumor, to measure the precise phosphorylation status of the tumors. Results obtained with SPECT-CT were similar to those obtained with planar scintigraphy. The tumor/normal muscle count ratios (TMR) were determined for all radiotracers used to treat the animals (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>). The TMR ratios were reported to be 1.5, 1.9, 4.0, and 6.0 for <sup>111</sup>In-EC-BSA (used to visualize blood flow), <sup>111</sup>In-EC-IgG<sub>1</sub> (negative control), <sup>111</sup>In-EC-APT, and <sup>111</sup>In-EC-Bcl-Abl (positive control), respectively.</p><p>With results obtained from this study (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>), the investigators concluded that imaging could be used to select a specific TK inhibitor for the treatment of certain cancer and to predict the treatment response in a clinical setting (<a class="bibr" href="#ECAPT111In.REF.5" rid="ECAPT111In.REF.5">5</a>).</p></div><div id="ECAPT111In.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=111In+EC+APT+Non+Primate+Mammal+studies" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="ECAPT111In.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=111In+EC+APT+Non+Human+Primate+studies" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div></div><div id="ECAPT111In.Human_Studies"><h2 id="_ECAPT111In_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=111In+EC+APT+Human+studies" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="ECAPT111In.Supplemental_Informa"><h2 id="_ECAPT111In_Supplemental_Informa_">Supplemental Information</h2><p>[<a href="/books/n/micad/disclaimer/?report=reader">Disclaimers</a>]</p></div><div id="ECAPT111In.References"><h2 id="_ECAPT111In_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ECAPT111In.REF.1">Finn R.S. Targeting Src in breast cancer. <span><span class="ref-journal">Ann Oncol. </span>2008;<span class="ref-vol">19</span>(8):1379–86.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18487549" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18487549</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ECAPT111In.REF.2">Pytel D., Sliwinski T., Poplawski T., Ferriola D., Majsterek I. Tyrosine kinase blockers: new hope for successful cancer therapy. <span><span class="ref-journal">Anticancer Agents Med Chem. </span>2009;<span class="ref-vol">9</span>(1):66–76.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19149483" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19149483</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ECAPT111In.REF.3">Muller B.A. Imatinib and its successors--how modern chemistry has changed drug development. <span><span class="ref-journal">Curr Pharm Des. </span>2009;<span class="ref-vol">15</span>(2):120–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19149608" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19149608</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ECAPT111In.REF.4">Gora-Tybor J., Robak T. Targeted drugs in chronic myeloid leukemia. <span><span class="ref-journal">Curr Med Chem. </span>2008;<span class="ref-vol">15</span>(29):3036–51.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19075651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19075651</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ECAPT111In.REF.5">Wu, J.Y., D.J. Yang, L.S. Angelo, S. Kohanim, and R. Kurzrock, Molecular imaging of Bcr-Abl phosphokinase in a xenograft model. Mol Cancer Ther, 2009. [<a href="/pmc/articles/PMC2679515/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2679515</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19258427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19258427</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ECAPT111In.REF.6">O'Hare T., Deininger M.W. Toward a cure for chronic myeloid leukemia. <span><span class="ref-journal">Clin Cancer Res. </span>2008;<span class="ref-vol">14</span>(24):7971–4.</span> [<a href="/pmc/articles/PMC2614298/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2614298</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19088011" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19088011</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK22989_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Arvind Chopra</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, NIH, Bethesda, MD 20894<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><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">March 12, 2009</span>; Last Update: <span itemprop="dateModified">April 6, 2009</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&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Chopra A. [111In]-Ethylenedicysteine-murine anti-phosphotyrosine antibody. 2009 Mar 12 [Updated 2009 Apr 6]. 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/Bomproamide111In/?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/AntiuPARpep111In/?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="figobECAPT111InT1"><div id="ECAPT111In.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK22989/table/ECAPT111In.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ECAPT111In.T1_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Chemical name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">[<sup>111</sup>In]-Ethylenedicysteine-murine anti-phosphotyrosine antibody<br /></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>111</sup>In-EC-APT<br /></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;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Agent Category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antibody</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bcr-Abl tyrosine kinase</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target Category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Enzyme</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Method of detection:</b>
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</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;">
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<b>Source of signal / contrast:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>111</sup>In</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Activation:</b>
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</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;">
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<b>Studies:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul class="simple-list"><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
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</div></li></ul>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Click here for the <a href="/entrez/viewer.fcgi?db=Nucleotide&dopt=GenBank&val=33318779" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nucleotide</a> and <a href="/sites/entrez?dopt=GenPept&cmd=Retrieve&db=protein&list_uids=148673890" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein</a> sequence of mouse (<i>Mus musculus</i>) tyrosine kinase.</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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