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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="Molecular Imaging and Contrast Agent Database (MICAD) [Internet]" /><meta name="citation_title" content="111In-Labeled DTPA conjugated monoclonal antibody 12A8 that targets the c-kit receptor" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2011/06/30" /><meta name="citation_author" content="Arvind Chopra" /><meta name="citation_pmid" content="21735592" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK56209/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="111In-Labeled DTPA conjugated monoclonal antibody 12A8 that targets the c-kit receptor" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="Arvind Chopra" /><meta name="DC.Date" content="2011/06/30" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK56209/" /><meta name="description" content="The c-kit (CD 117 antigen or stem cell factor ligand receptor) is a 145-kDa type III glycoprotein receptor tyrosine kinase (TK; encoded by the KIT proto-oncogene) that has a TK at the juxtamembrane position, which is activated when a ligand binds to the extracellular ligand-binding domain of the receptor (1). Almost 70% of gastrointestinal stromal tumors (GISTs) are known to overexpress a c-kit that has a mutation in exon 11 and produces a constitutively activated TK that promotes the survival and proliferation of cells and leads to the development of a malignant phenotype in the cells of the GISTs (1, 2). The biology and mutations of the c-kit gene and the detection, diagnosis, and chemotherapy of the cancerous GISTs are discussed in detail elsewhere (3, 4). An immunohistochemical method is commonly used to detect the overexpression of c-kit in GIST cancers, but this invasive technique is known to generate variable results (3, 5). In addition, investigators often use positron emission tomography (PET) with 18F-fluoro-deoxyglucose to detect, monitor, and assess the response of GISTs to chemotherapy, but this radiolabeled probe does not distinguish between GISTs and other cancerous tumors that have an epithelial or lymphatic origin (6)." /><meta name="og:title" content="111In-Labeled DTPA conjugated monoclonal antibody 12A8 that targets the c-kit receptor" /><meta name="og:type" content="book" /><meta name="og:description" content="The c-kit (CD 117 antigen or stem cell factor ligand receptor) is a 145-kDa type III glycoprotein receptor tyrosine kinase (TK; encoded by the KIT proto-oncogene) that has a TK at the juxtamembrane position, which is activated when a ligand binds to the extracellular ligand-binding domain of the receptor (1). Almost 70% of gastrointestinal stromal tumors (GISTs) are known to overexpress a c-kit that has a mutation in exon 11 and produces a constitutively activated TK that promotes the survival and proliferation of cells and leads to the development of a malignant phenotype in the cells of the GISTs (1, 2). The biology and mutations of the c-kit gene and the detection, diagnosis, and chemotherapy of the cancerous GISTs are discussed in detail elsewhere (3, 4). An immunohistochemical method is commonly used to detect the overexpression of c-kit in GIST cancers, but this invasive technique is known to generate variable results (3, 5). 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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="#__NBK56209_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK56209_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/Fab12A8111In/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/H2AXTat111In/" 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="_NBK56209_"><span class="title" itemprop="name"><sup>111</sup>In-Labeled DTPA conjugated monoclonal antibody 12A8 that targets the c-kit receptor</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"> [<sup>111</sup>In]12A8</div><p class="contrib-group"><span itemprop="author">Arvind Chopra</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK56209_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK56209_ai__"><div class="contrib half_rhythm"><span itemprop="author">Arvind Chopra</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, 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></div><p class="small">Created: <span itemprop="datePublished">June 9, 2011</span>; Last Update: <span itemprop="dateModified">June 30, 2011</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="IgG12A8111In.T.nc_chemical_name111inlabe" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56209/table/IgG12A8111In.T.nc_chemical_name111inlabe/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__IgG12A8111In.T.nc_chemical_name111inlabe_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-Labeled monoclonal antibody 12A8 that targets the c-kit receptor fragment<br /></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;">
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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]12A8<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;">Proto-oncogene c-Kit; tyrosine-protein kinase kit; Mast/stem cell growth factor receptor; CD117</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;">Receptor</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" />
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<i>In vitro</i>
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</div></li><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;">Structure not available in <a href="http://pubchem.ncbi.nlm.nih.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubChem</a>.</td></tr></tbody></table></div></div><div id="IgG12A8111In.Background"><h2 id="_IgG12A8111In_Background_">Background</h2><p>[<a href="/pubmed?term=c-kit&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The c-kit (CD 117 antigen or stem cell factor ligand receptor) is a 145-kDa type III glycoprotein receptor tyrosine kinase (TK; encoded by the <i>KIT</i> proto-oncogene) that has a TK at the juxtamembrane position, which is activated when a ligand binds to the extracellular ligand-binding domain of the receptor (<a class="bk_pop" href="#IgG12A8111In.REF.1">1</a>). Almost 70% of <a href="http://www.cancer.gov/cancertopics/pdq/treatment/gist/HealthProfessional" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gastrointestinal stromal tumors (GISTs)</a> are known to overexpress a c-kit that has a mutation in exon 11 and produces a constitutively activated TK that promotes the survival and proliferation of cells and leads to the development of a malignant phenotype in the cells of the GISTs (<a class="bk_pop" href="#IgG12A8111In.REF.1" data-bk-pop-others="IgG12A8111In.REF.2">1, 2</a>). The biology and mutations of the c-kit gene and the detection, diagnosis, and chemotherapy of the cancerous GISTs are discussed in detail elsewhere (<a class="bk_pop" href="#IgG12A8111In.REF.3" data-bk-pop-others="IgG12A8111In.REF.4">3, 4</a>). An immunohistochemical method is commonly used to detect the overexpression of c-kit in GIST cancers, but this invasive technique is known to generate variable results (<a class="bk_pop" href="#IgG12A8111In.REF.3" data-bk-pop-others="IgG12A8111In.REF.5">3, 5</a>). In addition, investigators often use positron emission tomography (PET) with <sup>18</sup>F-fluoro-deoxyglucose to detect, monitor, and assess the response of GISTs to chemotherapy, but this radiolabeled probe does not distinguish between GISTs and other cancerous tumors that have an epithelial or lymphatic origin (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>).</p><p>In an effort to develop a reliable method for the detection of GISTs, the <sup>111</sup>In-labeled anti–c-kit monoclonal antibody (mAb) 12A8 ([<sup>111</sup>In]12A8) was developed and evaluated for the detection of xenograft GISTs in nude mice with the use of single-photon emission computed tomography (SPECT) (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). Recently, the Fab fragment of mAb 12A8 was labeled with <sup>111</sup>In or with <sup>64</sup>Cu to obtain [<sup>111</sup>In]12A8 Fab or [<sup>64</sup>Cu]12A8 Fab, and the two probes were evaluated for the detection of tumors that express c-kit in nude mice (<a class="bk_pop" href="#IgG12A8111In.REF.2">2</a>). This chapter describes the <i>in vitro</i> and <i>in vivo</i> studies performed with [<sup>111</sup>In]12A8. Investigations conducted with [<sup>111</sup>In]12A8 Fab and [<sup>64</sup>Cu]12A8 Fab are discussed in separate chapters of MICAD (<a href="http://www.micad.nih.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.micad.nih.gov</a>) (<a class="bk_pop" href="#IgG12A8111In.REF.7" data-bk-pop-others="IgG12A8111In.REF.8">7, 8</a>).</p><div id="IgG12A8111In.Other_Sources_of_Informatio"><h3>Other Sources of Information</h3><p>c-kit–Related chapters in <a href="/books/?term=c-kit+AND+micad%5Bbook%5D&view=chapter&p%24a=&p%24l=PBooksLayout&p%24st=books" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MICAD</a></p><p>Human c-kit (also known as Hardy-Zuckerman 4 feline sarcoma viral oncogene-like protein (KIT)) <a href="/nuccore/HM015525.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein and mRNA</a> sequence (Source: NCBI GenBank)</p><p><a href="/nuccore?Db=gene&Cmd=retrieve&dopt=full_report&list_uids=3815" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Gene</a> (human c-kit; Gene ID: 3815)</p><p>c-kit in <a href="/omim?term=c-kit" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Online Mendelian Inheritance in Man (OMIM)</a></p><p><a href="http://pid.nci.nih.gov/search/pathway_landing.shtml?what=graphic&jpg=on&pathway_id=200175&source=NATURE&output-format=graphic&ppage=1&genes_a=3815" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Signaling events</a> mediated by c-kit (Source: Pathways Interaction Database)</p><p>c-kit–Related <a href="http://clinicaltrials.gov/ct2/results?term=c-kit" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">clinical trials</a></p><p>Information on c-kit in <a href="/pcassay/?term=c-kit" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubChem Bioassay</a></p></div></div><div id="IgG12A8111In.Synthesis"><h2 id="_IgG12A8111In_Synthesis_">Synthesis</h2><p>[<a href="/pubmed?term=111In-12A8%20synthesis&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Two clones of the c-kit mAb (12A8 and 41A11) were obtained from commercial sources and radioiodinated with <sup>125</sup>I using the chloramine-T method as described by Sogawa et al. (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). The specific activities of the labeled mAbs ranged from 277.5 to 555.0 kBq/μg (7.5 to 15 μCi/μg). In addition, 12A8 was labeled with <sup>125</sup>I using 3'-<sup>125</sup>I-iodohippuryl <i>N</i>-maleoyl-<span class="small-caps">l</span>-lysine (HML) to obtain [<sup>125</sup>I]HML-12A8. The radiochemical yield of purified [<sup>125</sup>I]HML-12A8 was ~37%, with a specific activity of ~11.8 kBq/μg (~0.32 μCi/μg).</p><p>The 12A8 and 41A11 mAbs were conjugated with <i>N</i>-[(<i>R</i>)-2-amino-3-(<i>p</i>-isothiocyanato-phenyl)propyl]-<i>trans</i>-(<i>S</i>,<i>S</i>)-cyclohexane-1,2-triaminepentaacetic acid (DTPA) and labeled with <sup>111</sup>In to generate [<sup>111</sup>In]12A8 and [<sup>111</sup>In]41A11 as detailed elsewhere (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). The DTPA:mAb ratio and the specific activity of the two labeled mAbs were reported to be 2.5 and ~111 kBq/μg (3 μCi/μg), respectively.</p><p>For use as an isotype-matched control, a non-specific IgG was also labeled with <sup>125</sup>I and <sup>111</sup>In as described above (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>).</p></div><div id="IgG12A8111In.In_Vitro_Studies_Testing_in"><h2 id="_IgG12A8111In_In_Vitro_Studies_Testing_in_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/pubmed?term=111In-12A8%20in%20vitro%20studies&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>All <i>in vitro</i> studies were performed with HEK293-c-kit-K642E cells (human embryonic kidney cells that were transfected with and stably express a mutated c-kit gene) (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). From cell-binding assays with [<sup>125</sup>I]12A8 IgG, [<sup>125</sup>I]HML-12A8 IgG, [<sup>111</sup>In]12A8 IgG, [<sup>125</sup>I]41A11 IgG, and [<sup>111</sup>In]41A11 IgG, it was determined that the immunoreactive fractions of these labeled mAbs were 90.8%, 83.6%, 86.3%, 86.4%, and 69.0%, respectively. Competitive binding assays showed that the dissociation constants of these mAbs for 2.4–7.9 × 10<sup>4</sup> binding sites on the cells were 3.9 × 10<sup>9</sup>, 7.1 × 10<sup>9</sup>, 2.2 × 10<sup>9</sup>, 4.0 × 10<sup>9</sup>, and 3.1 × 10<sup>9</sup> M−<sup>1</sup>, respectively. Cell internalization assays, in which the mAbs were labeled with <sup>125</sup>I or <sup>111</sup>In and incubated with the cells on ice for 1 h, revealed that ~80% of the label was associated with the cell membrane; however, 50% of the label was internalized by the cells and there was a steady decrease in the membrane-associated tracer when the incubation was performed for 3 h at 37°C. The investigators also observed that after 3 h at 37°C, only the cells incubated with [<sup>125</sup>I]12A8 IgG and [<sup>125</sup>I]HML-12A8 IgG lost internalized radioactivity and showed a simultaneous increase in the amount of label in the cell growth medium. After >21 h at 37°C, the amounts of internalized radioactivity in cells incubated with [<sup>111</sup>In]12A8 IgG , [<sup>125</sup>I]12A8 IgG, and [<sup>125</sup>I]HML-12A8 IgG were 81.1%, 60.4%, and 16.8%, respectively. Although the data were not presented in the publication, similar observations were reported for the labeled 41A11 mAb (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>).</p></div><div id="IgG12A8111In.Animal_Studies"><h2 id="_IgG12A8111In_Animal_Studies_">Animal Studies</h2><div id="IgG12A8111In.Rodents"><h3>Rodents</h3><p>[<a href="/pubmed?term=111In-12A8%20rodentia&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The biodistribution patterns of [<sup>125</sup>I]12A8 IgG, [<sup>125</sup>I]HML-12A8 IgG, and [<sup>111</sup>In]12A8 IgG were studied in nude mice bearing HEK293-c-kit-K642E cell xenograft tumors as described by Sogawa et al. (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). The animals (<i>n</i> = 5 mice/group) were intravenously injected with 37 kBq (1 μCi) <sup>125</sup>I- or <sup>111</sup>In-labeled 12A8 IgG (protein concentration was adjusted to 5 μg/mouse by the addition of unlabeled 12A8) and euthanized at 24, 48, and 96 h postinjection (p.i.) to determine the amount of radioactivity accumulated in the tumors and the major organs. All data were reported as percent of injected dose per gram tissue (% ID/g). The investigators observed similar biodistribution patterns in the tumor for the two radioiodinated 12A8 mAbs in the animals. With [<sup>125</sup>I]12A8 IgG , the maximum accumulation of radioactivity was 1.5 ± 0.6% ID/g at 24 h p.i. and decreased thereafter. The tumor/blood (T/B) ratios for [<sup>125</sup>I]12A8 IgG were low at all time points (0.2, 0.1, and 0.2 at 24, 48, and 96 h p.i., respectively), and the T/B ratios for [<sup>125</sup>I]HML-12A8 IgG were even lower. No blocking studies were reported.</p><p>With [<sup>111</sup>In]12A8 IgG , the accumulation of radioactivity in the tumors increased from 6.6 ± 2.0% ID/g at 24 h to 9.2 ± 3.5% ID/g at 96 h p.i., and during the same period the T/B ratio increased from 0.6 at 24 h to 1.3 at 96 h p.i (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). The uptake values of [<sup>111</sup>In]12A8 IgG in the liver, spleen, and kidney were higher than those of [<sup>125</sup>I]12A8 IgG in the same organs. In comparison, the tumor uptake of the non-specific <sup>111</sup>In-labeled IgG remained between 2.9% ID/g and 3.3% ID/g from 24 h to 96 h p.i., and the T/B ratio was 0.1 at 96 h p.i. The biodistribution of [<sup>111</sup>In]12A8 IgG was also investigated in nude mice bearing GIST822 cell xenograft tumors (human GIST cells described by Tuveson et al. (<a class="bk_pop" href="#IgG12A8111In.REF.9">9</a>)) (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). At 96 h p.i., the tumor uptake of radioactivity was 5.3% ID/g with a T/B ratio of 0.9, and these values were lower than those observed with the HEK293-c-kit-K642E cell xenograft tumors at the same time point. From these results, the investigators concluded that the labeled mAb bound specifically to the c-kit expressed on the GIST tumor cells. No blocking studies were reported.</p><p>Gamma planar and SPECT images were acquired from mice bearing xenograft tumors derived from HEK293-c-kit-K642E cells (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). Planar imaging was performed on one anesthetized animal at 24, 48, and 96 h p.i. The tumor outline was first visible at 48 h p.i. and became clearly visible at 96 h p.i. SPECT images taken at 96 h p.i. showed that the tumor was clearly visible in the transverse, coronal, and saggital views of the animal. No blocking studies were reported.</p><p>From these studies, the investigators concluded that radioiodinated anti–c-kit mAbs were not suitable for the visualization of tumors that express c-kit in mice because the labeled mAbs were dehaloginated after internalization by the cells (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>). However, the tumors positive for c-kit showed a high uptake of radioactivity when exposed to an <sup>111</sup>In-labeled anti–c-kit mAb, and this radionuclide was suitable for the visualization of the tumors with SPECT imaging (<a class="bk_pop" href="#IgG12A8111In.REF.6">6</a>).</p></div><div id="IgG12A8111In.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/pubmed?term=111In-12A8%20Non-Primate%20Mammals&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publications are currently available.</p></div><div id="IgG12A8111In.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/pubmed?term=111In-12A8%20Non-Human%20Primates&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publications are currently available.</p></div></div><div id="IgG12A8111In.Human_Studies"><h2 id="_IgG12A8111In_Human_Studies_">Human Studies</h2><p>[<a href="/pubmed?term=111In-12A8%20Human%20Studies&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publications are currently available.</p></div><div id="IgG12A8111In.Supplemental_Information"><h2 id="_IgG12A8111In_Supplemental_Information_">Supplemental Information</h2><p>[<a href="/books/n/micad/disclaimer/">Disclaimers</a>]</p><p>No information is currently available.</p></div><div id="IgG12A8111In.References"><h2 id="_IgG12A8111In_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.1">Aubin F., Blanke C.D.
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<em>Metastatic gastrointestinal stromal tumors.</em>
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<span><span class="ref-journal">Cancer Chemother Pharmacol. </span>2011;<span class="ref-vol">67</span> Suppl 1:S9–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21116628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21116628</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.2">Yoshida C. et al.
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<em>Development of positron emission tomography probe of 64Cu-labeled anti-C-kit 12A8 Fab to measure protooncogene C-kit expression.</em>
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<span><span class="ref-journal">Nucl Med Biol. </span>2011;<span class="ref-vol">38</span>(3):331–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21492781" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21492781</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.3">Corless C.L., Heinrich M.C.
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<em>Molecular pathobiology of gastrointestinal stromal sarcomas.</em>
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<span><span class="ref-journal">Annu Rev Pathol. </span>2008;<span class="ref-vol">3</span>:557–86.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18039140" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18039140</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.4">Wang W.L. et al.
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<em>Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor.</em>
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<span><span class="ref-journal">Cancer Chemother Pharmacol. </span>2011;<span class="ref-vol">67</span> Suppl 1:S15–24.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21181476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21181476</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.5">Miettinen M., Lasota J.
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<em>KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation.</em>
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<span><span class="ref-journal">Appl Immunohistochem Mol Morphol. </span>2005;<span class="ref-vol">13</span>(3):205–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16082245" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16082245</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.6">Sogawa C. et al.
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<em>C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model.</em>
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<span><span class="ref-journal">Nucl Med Biol. </span>2010;<span class="ref-vol">37</span>(2):179–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20152717" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20152717</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.7">Chopra, A., <em>111In-labeled Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH2 (IMP-156).</em> Molecular Imaging and Contrast agent Database (MICAD) [database online]. National Library of Medicine, NCBI, Bethesda, MD, USA. Available from <a href="http://www.micad.nih.gov/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">www<wbr style="display:inline-block"></wbr>.micad.nih.gov</a>, 2004 -to current. [<a href="https://pubmed.ncbi.nlm.nih.gov/21834179" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21834179</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.8">Chopra, A., <em>64Cu-Labeled anti-c-kit monoclonal antibody 12A8 Fab fragment.</em> Molecular Imaging and Contrast agent Database (MICAD) [database online]. National Library of Medicine, NCBI, Bethesda, MD, USA. Available from <a href="http://www.micad.nih.gov/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">www<wbr style="display:inline-block"></wbr>.micad.nih.gov</a>, 2004 -to current. [<a href="https://pubmed.ncbi.nlm.nih.gov/21735589" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21735589</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="IgG12A8111In.REF.9">Tuveson D.A. et al.
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<em>STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.</em>
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<span><span class="ref-journal">Oncogene. </span>2001;<span class="ref-vol">20</span>(36):5054–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11526490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11526490</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: NBK56209</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/21735592" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">21735592</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/Fab12A8111In/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/H2AXTat111In/" 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/NBK56209/?report=reader">PubReader</a></li><li><a href="/books/NBK56209/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK56209" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK56209" style="display:none" title="Cite this Page"><div class="bk_tt">Chopra A. 111In-Labeled DTPA conjugated monoclonal antibody 12A8 that targets the c-kit receptor. 2011 Jun 9 [Updated 2011 Jun 30]. 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/NBK56209/pdf/Bookshelf_NBK56209.pdf">PDF version of this page</a> (138K)</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="#IgG12A8111In.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#IgG12A8111In.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#IgG12A8111In.In_Vitro_Studies_Testing_in" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#IgG12A8111In.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#IgG12A8111In.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#IgG12A8111In.Supplemental_Information" ref="log$=inpage&link_id=inpage">Supplemental Information</a></li><li><a href="#IgG12A8111In.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 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class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21735588" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (111)In-Labeled DTPA conjugated anti-c-kit monoclonal antibody 12A8 Fab fragment.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (111)In-Labeled DTPA conjugated anti-c-kit monoclonal antibody 12A8 Fab fragment.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Chopra A. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21735589" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (64)Cu-Labeled anti-c-kit monoclonal antibody 12A8 Fab fragment.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (64)Cu-Labeled anti-c-kit monoclonal antibody 12A8 Fab fragment.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Chopra A. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20698071" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (111)In-Labeled CHX-A”-DTPA conjugated monoclonal antibody (mAb) 806 targeting the epidermal growth factor receptor deletion variant de2-7 (EGFRvIII).</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span 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class="author">Chopra A. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=21735592" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=21735592" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" 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