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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/125/131I-Labeled anti-mucin-1 murine, chimeric or humanized antibody hPAM4" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2011/07/26" /><meta name="citation_author" content="Arvind Chopra" /><meta name="citation_pmid" content="21834178" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK57127/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="111In/125/131I-Labeled anti-mucin-1 murine, chimeric or humanized antibody hPAM4" /><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="2011/07/26" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK57127/" /><meta name="description" content="Mucins (MUC) are a distinct class of transmembrane glycoproteins (designated as MUC1, MUC3A, MUC3B, MUC4, etc.) that are expressed primarily by the glandular and ductal cells of the epithelium in the human body and are known to modulate the tumorigenicity, progression, and pathogenesis of different cancers (1). The structure, physiological function, and process of promoting the development of malignancies by MUCs, particularly MUC1 and MUC4, are discussed in detail by Bafna et al. (1). MUC1 has been shown to be characteristically overexpressed by pancreatic adenocarcinoma (PAC) cells and is not detectable in normal pancreatic ducts or other normal tissues, or during an incident of pancreatitis (2). Because it is detectable only in the serum of patients suffering from PAC, it was suggested recently that the MUC1 antigen can be used as a biomarker for the early detection this malignancy (3, 4)." /><meta name="og:title" content="111In/125/131I-Labeled anti-mucin-1 murine, chimeric or humanized antibody hPAM4" /><meta name="og:type" content="book" /><meta name="og:description" content="Mucins (MUC) are a distinct class of transmembrane glycoproteins (designated as MUC1, MUC3A, MUC3B, MUC4, etc.) that are expressed primarily by the glandular and ductal cells of the epithelium in the human body and are known to modulate the tumorigenicity, progression, and pathogenesis of different cancers (1). The structure, physiological function, and process of promoting the development of malignancies by MUCs, particularly MUC1 and MUC4, are discussed in detail by Bafna et al. (1). MUC1 has been shown to be characteristically overexpressed by pancreatic adenocarcinoma (PAC) cells and is not detectable in normal pancreatic ducts or other normal tissues, or during an incident of pancreatitis (2). Because it is detectable only in the serum of patients suffering from PAC, it was suggested recently that the MUC1 antigen can be used as a biomarker for the early detection this malignancy (3, 4)." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK57127/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-micad-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/micad/hPAM4InI/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK57127/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
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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="#__NBK57127_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK57127_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/BNDTPA111In/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/HE3H6Zher2342InTcI/" 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="_NBK57127_"><span class="title" itemprop="name"><sup>111</sup>In/<sup>125/131</sup>I-Labeled anti-mucin-1 murine, chimeric or humanized antibody hPAM4</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"> [<sup>111</sup>In/<sup>125/131</sup>I]-hPAM4</div><p class="contrib-group"><span itemprop="author">Arvind Chopra</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK57127_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK57127_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 16, 2011</span>; Last Update: <span itemprop="dateModified">July 26, 2011</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="hPAM4InI.T.nc_chemical_name111in125131il" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK57127/table/hPAM4InI.T.nc_chemical_name111in125131il/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hPAM4InI.T.nc_chemical_name111in125131il_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/<sup>125/131</sup>I-Labeled anti-mucin-1 murine, chimeric or humanized antibody hPAM4<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/<sup>125/131</sup>I]-hPAM4<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;">Mucin 1 (MUC1)</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;">Antigen</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 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/<sup>125/131</sup>I</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><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Humans
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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="hPAM4InI.Background"><h2 id="_hPAM4InI_Background_">Background</h2><p>[<a href="/pubmed?term=hPAM4&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Mucins (MUC) are a distinct class of transmembrane glycoproteins (designated as MUC1, MUC3A, MUC3B, MUC4, etc.) that are expressed primarily by the glandular and ductal cells of the epithelium in the human body and are known to modulate the tumorigenicity, progression, and pathogenesis of different cancers (<a class="bk_pop" href="#hPAM4InI.REF.1">1</a>). The structure, physiological function, and process of promoting the development of malignancies by MUCs, particularly MUC1 and MUC4, are discussed in detail by Bafna et al. (<a class="bk_pop" href="#hPAM4InI.REF.1">1</a>). MUC1 has been shown to be characteristically overexpressed by pancreatic <a href="http://www.cancer.gov/dictionary?cdrid=46216" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">adenocarcinoma</a> (PAC) cells and is not detectable in normal pancreatic ducts or other normal tissues, or during an incident of pancreatitis (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>). Because it is detectable only in the serum of patients suffering from PAC, it was suggested recently that the MUC1 antigen can be used as a biomarker for the early detection this malignancy (<a class="bk_pop" href="#hPAM4InI.REF.3" data-bk-pop-others="hPAM4InI.REF.4">3, 4</a>).</p><p>The majority of individuals suffering from PAC do not survive for more than 1 year after diagnosis, and <1% of these patients live beyond 5 years (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). Although surgical resection of the cancer is a possible treatment for this disease, only 10%–25% of the patients are considered suitable for this treatment because, by the time that the neoplasm is detected, the malignancy has metastasized and the tumor load in the patient is too high to warrant surgery (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). Patients with nonresectable PAC are treated either with <a href="http://www.cancer.gov/cancertopics/druginfo/gemcitabinehydrochloride" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gemcitabine</a> or radiotherapy; however, these treatments are not curative and only prolong survival and improve the quality of life of the patient (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). The detection of this invasive cancer at an early stage would facilitate proper staging of the disease, which could be followed either by surgical resection of the tumor or the initiation of a vigorous treatment regimen that could possibly improve patient prognosis (<a class="bk_pop" href="#hPAM4InI.REF.6">6</a>).</p><p>More than a decade ago, a <sup>131</sup>I-labeled murine monoclonal antibody, PAM4 ([<sup>131</sup>I]-mPAM4), directed against a mucin (later identified to be MUC1 (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>)) was reported to detect human xenograft PAC tumors in mice with high specificity and, compared to controls, significantly extended the survival time of the animals when used for radiotherapy of the cancer (<a class="bk_pop" href="#hPAM4InI.REF.7" data-bk-pop-others="hPAM4InI.REF.8 hPAM4InI.REF.9">7-9</a>). In a preliminary study, [<sup>131</sup>I]-PAM4 was demonstrated to detect the primary and the metastasized pancreatic carcinoma tumors in humans, and there was a low nonspecific uptake of the tracer in the liver, spleen, and bone marrow of the patients (<a class="bk_pop" href="#hPAM4InI.REF.10">10</a>). In another study, a chimeric form of PAM4 (cPAM4) was labeled with <sup>125</sup>I and <sup>111</sup>In to obtain [<sup>125</sup>I]-cPAM4 and [<sup>111</sup>In]-cPAM4, respectively, and the biodistribution of these labeled mAbs was investigated in mice bearing human xenograft PAC tumors (<a class="bk_pop" href="#hPAM4InI.REF.11">11</a>). Recently, Gulec et al. studied the biodistribution of <sup>111</sup>In-labeled humanized PAM4 ( [<sup>111</sup>In]-hPAM4) in a phase I clinical trial (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>).</p><div id="hPAM4InI.Other_Sources_of_Information"><h3>Other Sources of Information</h3><p>Other anti-MUC1 antibody chapters in <a href="/books/?term=MUC1%20AND%20micad%5Bbook%5D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MICAD</a></p><p>Chapters on radiolabeled antibodies in <a href="/books/?term=radiolabeled%20antibodies%20AND%20micad%5Bbook%5D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MICAD</a></p><p>Chimeric antibodies [<a href="/pubmed?term=chimeric%20antibody&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Humanized antibodies [<a href="/pubmed?term=humanized%20antibodies&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p><a href="/nuccore/NM_002456.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Protein and mRNA sequence</a> of human MUC1, transcript variant 1</p><p><a href="/omim?term=MUC1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MUC1</a> in Online Mendelian Inheritance in Man database (OMIM)</p><p>Information regarding MUC1 in <a href="http://geneticassociationdb.nih.gov/cgi-bin/tableview.cgi?table=geneview&cond=GENE%20like%20%27MUC1%27" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Genetic Association Database</a></p><p><a href="/omim?Db=gene&DbFrom=omim&Cmd=Link&LinkName=omim_gene&LinkReadableName=Gene&IdsFromResult=158340" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Gene information</a> of MUC1 (Gene ID: 4582)</p><p>MUC1 related <a href="http://clinicaltrials.gov/ct2/results?term=MUC1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Clinical trials</a></p></div></div><div id="hPAM4InI.Synthesis"><h2 id="_hPAM4InI_Synthesis_">Synthesis</h2><p>[<a href="/pubmed?term=Radiolabeled-PAM4%20synthesis&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The mPAM4 (<a class="bk_pop" href="#hPAM4InI.REF.8">8</a>), cPAM4 (<a class="bk_pop" href="#hPAM4InI.REF.11">11</a>), and hPAM4 (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>) used in the different investigations were obtained from a commercial source.</p><p>mPAM4 was labeled with <sup>131</sup>I using the chloramine-T method, and the specific activity (SA) of the labeled antibody was reported to be 259–444 kBq/μg (7–12 μCi/μg) (<a class="bk_pop" href="#hPAM4InI.REF.7">7</a>). The [<sup>131</sup>I]-mPAM4 preparation contained <3% free <sup>131</sup>I and no aggregates as determined with thin-layer chromatography (TLC). Gold et al. labeled mPAM4 with <sup>131</sup>I using the Iodo-Gen procedure (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). The labeling efficiency of this method was reported to be 90%; the SA of the labeled mAb was 370–555 MBq/mg (10–15 mCi/mg), and the final preparation contained <5% unbound radioactivity as determined with high-performance liquid chromatography (HPLC) (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>).</p><p>cPAM4 was labeled with <sup>125</sup>I using the chloramine-T procedure as described above (<a class="bk_pop" href="#hPAM4InI.REF.11">11</a>). The labeled mAb had a SA of 365.6–455 kBq/μg (9.88–12.3 μCi/μg) and contained <5% unbound <sup>125</sup>I and <8% aggregates.</p><p>cPAM4 was labeled with <sup>111</sup>In after conjugation of the mAb to 1,4,7,10-tetraazacyclododecane-<i>N</i>,<i>N’</i>,<i>N’’</i>,<i>N’’’</i>-tetraacetic acid (DOTA) (<a class="bk_pop" href="#hPAM4InI.REF.11">11</a>), and the DOTA:cPAM4 ratio of the conjugate was reported in another publication to be 3.3 (<a class="bk_pop" href="#hPAM4InI.REF.12">12</a>). The SA of [<sup>111</sup>In]-cPAM4 was reported to vary from 200 kBq/μg (5.41 μCi/μg) to 48.1–133.2 MBq/mg (1.3–3.6 mCi/mg) and contained <1.7% unbound radionuclides and <1% aggregates (<a class="bk_pop" href="#hPAM4InI.REF.5" data-bk-pop-others="hPAM4InI.REF.11 hPAM4InI.REF.12">5, 11, 12</a>).</p><p>The biodistribution and tumor targeting of [<sup>111</sup>In]-hPAM4 was investigated in patients suffering from pancreatic cancer in a phase I clinical trial (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>). Although the [<sup>111</sup>In]-hPAM4 preparation used in the clinical investigation was reported to contain <10% free radionuclide as determined with instant TLC, the SA of the labeled antibody was not reported.</p></div><div id="hPAM4InI.In_Vitro_Studies_Testing_in_Cel"><h2 id="_hPAM4InI_In_Vitro_Studies_Testing_in_Cel_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/pubmed?term=PAM4%20in%20vitro&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="hPAM4InI.Animal_Studies"><h2 id="_hPAM4InI_Animal_Studies_">Animal Studies</h2><div id="hPAM4InI.Rodents"><h3>Rodents</h3><p>[<a href="/pubmed?term=PAM4%20rodentia&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The biodistribution of [<sup>131</sup>I]-mPAM4 was investigated in <i>nu/nu</i> mice bearing xenograft orthotopic <a href="http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=HTB-79&Template=cellBiology" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CaPan-1 cell</a> tumors as described by Alisauskus et al. (<a class="bk_pop" href="#hPAM4InI.REF.7">7</a>). The mice (<i>n</i> = 5–8 animals/group) were injected with 25 μCi [<sup>131</sup>I]-mPAM4 (route of injection was not reported) and euthanized at various time points from 1 d to 14 d postinjection (p.i.). All major organs were removed from the animals, and the amount of accumulated radioactivity in the tissues was determined. Data obtained from this study were presented as the percentage of injected dose per gram tissue (% ID/g). The amount of radioactivity in the tumor was shown to decrease steadily from ~15% ID/g at day 1 p.i. to ~4% ID/g at day 14 p.i. In all other organs, the accumulation of radioactivity was between ~2% ID/g (kidneys) and ~5% ID/g (both spleen and blood) on day 1 p.i., and accumulation reduced to <1% ID/g by day 14 p.i. in all the organs. <i>Ex vivo</i> microautoradigraphy of 5-μm tumor sections showed that the radioactivity was confined within the tumors and no tracer was detected in the surrounding normal tissues (<a class="bk_pop" href="#hPAM4InI.REF.7">7</a>). No blocking studies were reported.</p><p>In another study, Cardillo et al. investigated the biodistribution of [<sup>125</sup>I]-cPAM4 in athymic mice bearing CaPan-1 cell tumors (<a class="bk_pop" href="#hPAM4InI.REF.11">11</a>). The biodistribution pattern of the <sup>125</sup>I-labeled chimeric mAb was shown to be similar to that of [<sup>131</sup>I]-mPAM4 as described above.</p><p>Gold et al. studied the biodistribution of [<sup>111</sup>In]-cPAM4 (used as a surrogate for immunotherapeutic <sup>90</sup>Y-labeled cPAM4) in athymic mice bearing similarly sized CaPan-1 cell tumors (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). The animals (<i>n</i> = at least 8 mice/group) were injected with 25 μCi labeled cPAM4 for a total of 25 μg protein/animal, and the preparation also contained the unlabeled chimeric antibody. The mice were euthanized on days 1, 4 and 7 p.i., and all major organs were removed to determine the amount of accumulated radioactivity. The uptake of radioactivity by the tumor was ~25% ID/g on day 1 p.i., increased to ~40% ID/g by day 4 p.i., and decreased to ~25% ID/g on day 7 p.i. During the same period, the accumulation of the tracer in all major organs was between ~2% ID/g (normal pancreas) and ~10% ID/g (blood) on day 1 p.i., and between 2% ID/g (blood) and ~7% ID/g (liver) on day 7 p.i. The amount of tracer in the liver remained constant during the entire period of the study, indicating that the radioactivity was excreted primarily through the hepatobiliary route. The estimated potential radiation dose received by the tumor, the tumor/blood radiation ratio, and the maximum tolerated dose of [<sup>90</sup>Y]-cPAM4 for the animals were described elsewhere (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). Other investigators reported a similar biodistribution pattern for [<sup>111</sup>In]-cPAM4 in athymic <i>nu/nu</i> mice bearing CaPan-1 cell tumors (<a class="bk_pop" href="#hPAM4InI.REF.11">11</a>).</p><p>In another study, mice bearing subcutaneous CaPan-1 cell tumors were injected with [<sup>111</sup>In]-cPAM4, and whole-body immunoscintigraphic images were acquired from the animals (<i>n</i> = 2 mice) at various time points as described by Cardillo et al. (<a class="bk_pop" href="#hPAM4InI.REF.12">12</a>). At 24 h p.i., high background levels of the tracer were observed in the thoracic and abdominal areas of the animals, and the tumors on the animals became visible clearly only at 48 h p.i., indicating a slow clearance of radioactivity from the mice (<a class="bk_pop" href="#hPAM4InI.REF.12">12</a>). In another part of the same study (<i>n</i> = 14 animals), the tumor/blood, tumor/liver, tumor/kidney, and tumor/normal pancreas radioactivity uptake ratios were reported to be 2.4 ± 1.0, 3.5 ± 1.6, 5.9 ± 1.3, and 18.6 ± 8.2, respectively.</p></div><div id="hPAM4InI.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/pubmed?term=PAM4%20Non-Primate%20Mammals&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="hPAM4InI.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/pubmed?term=PAM4%20Non-Human%20Primates&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="hPAM4InI.Human_Studies"><h2 id="_hPAM4InI_Human_Studies_">Human Studies</h2><p>[<a href="/pubmed?term=PAM4%20Human%20Studies&cmd=DetailsSearch" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Two patients with histologically confirmed metastatic pancreatic cancer were injected with [<sup>131</sup>I]-mPAM4; one patient received 270 MBq (7.3 mCi) [<sup>131</sup>I]-mPAM4 in a protein dose of 0.6 mg, and the other patient received 315 MBq (8.5 mCi) [<sup>131</sup>I]-mPAM4 in a protein dose of 0.6 mg (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). Blood samples taken from the two patients showed that the clearance of radioactivity from this tissue was biexponential. The circulating half-life of the tracer in the early component of the curve was 1.9 h in the patient with the smaller dose and 4.6 h in the patient with the larger dose; in the late component the half-life values were 28.6 h and 39.2 h, respectively. HPLC analysis of the plasma obtained from these patients at 24 h p.i. showed the presence of 66%–78% <sup>131</sup>I in the small molecular weight fraction, indicating that mPAM4 was catabolized in the blood within 24 h p.i. Scintigraphy was performed on a patient injected with [<sup>131</sup>I]-mPAM4 (the patient had previously undergone chemotherapy and radiotherapy for the treatment of PAC), and clear uptake of the tracer was observed in tumors on the left hepatic lobe and in the mid-abdomen area of the patient (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). Similarly, tumors were also detected in posterior and anterior planar images acquired from a second patient injected with the radioiodinated mAb (<a class="bk_pop" href="#hPAM4InI.REF.5">5</a>). From this study, the investigators concluded that mPAM4 specifically targeted pancreatic cancer tumors in the patients.</p><p>In a phase I clinical study to evaluate the efficacy of [<sup>90</sup>Y]-hPAM4 for the treatment of PAC, 21 patients (4 patients with stage III, locally advanced disease; 17 patients with stage IV metastatic disease) were administered a slow intravenous injection of [<sup>111</sup>In]-hPAM4 to investigate the biodistribution of the tracer (a surrogate for the <sup>90</sup>Y-labeled homolog) in the individuals (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>). The patients received 3–5 mCi of the label, and the total protein content of each dose, including the unlabeled hPAM4, was 10 mg (for 6 patients) and 100 mg (for 16 patients). Starting at 4 h p.i., repeat whole-body planar scintigraphic images were acquired from the patients over 7 days. Pancreatic tumors were clearly visible at 24 h p.i. (only a representative image was presented (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>)), and the visibility was progressively prominent on the subsequent images. From a review of the various images obtained from this study, the investigators concluded there was no qualitative difference was apparent in the biodistribution of [<sup>111</sup>In]-hPAM4 at the two doses (10 and 100 mg total hPAM4), the humanized mAb showed a normal biodistribution in the patients suffering from PAC and was suitable for the scintigraphic visualization of PAC tumors in humans (<a class="bk_pop" href="#hPAM4InI.REF.2">2</a>).</p></div><div id="hPAM4InI.Supplemental_Information"><h2 id="_hPAM4InI_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="hPAM4InI.NIH_Support"><h2 id="_hPAM4InI_NIH_Support_">NIH Support</h2><p>Studies described in this chapter were supported in part by grants CA39841, CA43218, and CA54425 from the National Institutes of Health.</p></div><div id="hPAM4InI.References"><h2 id="_hPAM4InI_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.1">Bafna S., Kaur S., Batra S.K.
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<em>Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells.</em>
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<span><span class="ref-journal">Oncogene. </span>2010;<span class="ref-vol">29</span>(20):2893–904.</span> [<a href="/pmc/articles/PMC2879972/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2879972</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20348949" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20348949</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.2">Gulec S.A., Cohen S.J., Pennington K.L., Zuckier L.S., Hauke R.J., Horne H., Wegener W.A., Teoh N., Gold D.V., Sharkey R.M., Goldenberg D.M.
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<em>Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial.</em>
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<span><span class="ref-journal">Clin Cancer Res. </span>2011;<span class="ref-vol">17</span>(12):4091–100.</span> [<a href="/pmc/articles/PMC4048986/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4048986</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21527562" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21527562</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.3">Gold D.V., Karanjawala Z., Modrak D.E., Goldenberg D.M., Hruban R.H.
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<em>PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma.</em>
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<span><span class="ref-journal">Clin Cancer Res. </span>2007;<span class="ref-vol">13</span>(24):7380–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18094420" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18094420</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.4">Gold D.V., Modrak D.E., Ying Z., Cardillo T.M., Sharkey R.M., Goldenberg D.M.
|
||
<em>New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis.</em>
|
||
<span><span class="ref-journal">J Clin Oncol. </span>2006;<span class="ref-vol">24</span>(2):252–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16344318" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16344318</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.5">Gold D.V., Cardillo T., Goldenberg D.M., Sharkey R.M.
|
||
<em>Localization of pancreatic cancer with radiolabeled monoclonal antibody PAM4.</em>
|
||
<span><span class="ref-journal">Crit Rev Oncol Hematol. </span>2001;<span class="ref-vol">39</span>(1-2):147–54.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11418312" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11418312</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.6">Gold D.V., Goggins M., Modrak D.E., Newsome G., Liu M., Shi C., Hruban R.H., Goldenberg D.M.
|
||
<em>Detection of early-stage pancreatic adenocarcinoma.</em>
|
||
<span><span class="ref-journal">Cancer Epidemiol Biomarkers Prev. </span>2010;<span class="ref-vol">19</span>(11):2786–94.</span> [<a href="/pmc/articles/PMC2976815/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2976815</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20810605" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20810605</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.7">Alisauskus R., Wong G.Y., Gold D.V.
|
||
<em>Initial studies of monoclonal antibody PAM4 targeting to xenografted orthotopic pancreatic cancer.</em>
|
||
<span><span class="ref-journal">Cancer Res. </span>1995;<span class="ref-vol">55</span>(23) Suppl:5743s–5748s.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7493339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7493339</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.8">Gold D.V., Alisauskas R., Sharkey R.M.
|
||
<em>Targeting of xenografted pancreatic cancer with a new monoclonal antibody, PAM4.</em>
|
||
<span><span class="ref-journal">Cancer Res. </span>1995;<span class="ref-vol">55</span>(5):1105–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7866995" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7866995</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.9">Gold D.V., Cardillo T., Vardi Y., Blumenthal R.
|
||
<em>Radioimmunotherapy of experimental pancreatic cancer with 131I-labeled monoclonal antibody PAM4.</em>
|
||
<span><span class="ref-journal">Int J Cancer. </span>1997;<span class="ref-vol">71</span>(4):660–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9178823" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9178823</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.10">Mariani G., Molea N., Bacciardi D., Boggi U., Fornaciari G., Campani D., Salvadori P.A., Giulianotti P.C., Mosca F., Gold D.V. et al.
|
||
<em>Initial tumor targeting, biodistribution, and pharmacokinetic evaluation of the monoclonal antibody PAM4 in patients with pancreatic cancer.</em>
|
||
<span><span class="ref-journal">Cancer Res. </span>1995;<span class="ref-vol">55</span>(23) Suppl:5911s–5915s.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7493369" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7493369</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.11">Cardillo T.M., Ying Z., Gold D.V.
|
||
<em>Therapeutic advantage of (90)yttrium- versus (131)iodine-labeled PAM4 antibody in experimental pancreatic cancer.</em>
|
||
<span><span class="ref-journal">Clin Cancer Res. </span>2001;<span class="ref-vol">7</span>(10):3186–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11595713" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11595713</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="hPAM4InI.REF.12">Cardillo T.M., Karacay H., Goldenberg D.M., Yeldell D., Chang C.H., Modrak D.E., Sharkey R.M., Gold D.V.
|
||
<em>Improved targeting of pancreatic cancer: experimental studies of a new bispecific antibody, pretargeting enhancement system for immunoscintigraphy.</em>
|
||
<span><span class="ref-journal">Clin Cancer Res. </span>2004;<span class="ref-vol">10</span>(10):3552–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15161715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15161715</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: NBK57127</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/21834178" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">21834178</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/BNDTPA111In/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/HE3H6Zher2342InTcI/" title="Next page in this title">Next ></a></div></div></div></div>
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<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK57127&db=books">Share</a></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/NBK57127/?report=reader">PubReader</a></li><li><a href="/books/NBK57127/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK57127" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK57127" style="display:none" title="Cite this Page"><div class="bk_tt">Chopra A. 111In/125/131I-Labeled anti-mucin-1 murine, chimeric or humanized antibody hPAM4. 2011 Jun 16 [Updated 2011 Jul 26]. 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/NBK57127/pdf/Bookshelf_NBK57127.pdf">PDF version of this page</a> (149K)</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="#hPAM4InI.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#hPAM4InI.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#hPAM4InI.In_Vitro_Studies_Testing_in_Cel" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#hPAM4InI.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#hPAM4InI.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#hPAM4InI.Supplemental_Information" ref="log$=inpage&link_id=inpage">Supplemental Information</a></li><li><a href="#hPAM4InI.NIH_Support" ref="log$=inpage&link_id=inpage">NIH Support</a></li><li><a href="#hPAM4InI.References" ref="log$=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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europium</option><option value="(166Ho OR 67Ga OR 68Ga OR 123I OR 124I OR 125I)">Radionuclides</option></optgroup><optgroup label="Optical agents"><option value="("Fluorescent dyes" OR protein)">Fluorescent dyes or proteins</option><option value=""Luminescent agents"">Luminescent agents</option><option value="(Metals OR Metal OR Gold OR Au)">Metals (Au)</option><option value="Nanotubes">Nanotubes</option><option value=""Quantum dots"">Quantum dots</option></optgroup><optgroup label="PET radionuclides"><option value="("Arsenic 74" OR 74As)">Arsenic-74</option><option value="("Bromine 76" OR 76Br)">Bromine-76</option><option value="("Carbon 11" OR 11C)">Carbon-11</option><option value="(Copper-60 OR Copper-61 OR Copper-62 OR Copper-64 OR 60Cu OR 61Cu OR 62Cu OR 64Cu)">Copper-60, 61, 62, 64</option><option value="("Fluorine 18" OR 18F)">Fluorine-18</option><option value="(Gallium-68 OR 68Ga)">Gallium-68</option><option value="("Iodine 124" OR 124I)">Iodine-124</option><option 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receptor-antibody OR antibody-receptor)">Receptors</option><option value="transporter">Transporters</option><option value="non-targeted">Non-targeted</option><option value=""nucleic acid"">Nucleic acids</option><option value="(non-targeted OR "unknown binding site")">Others</option></select></div></div><div><input id="__micad_btn_1" type="radio" name="stage" value="vitro" /><label for="__micad_btn_1"><i>In vitro</i></label><input id="__micad_btn_2" type="radio" name="stage" value="rodents" /><label for="__micad_btn_2">Rodents</label><input id="__micad_btn_3" type="radio" name="stage" value="mammals" /><label for="__micad_btn_3">Non-primate non-rodent mammals</label><br /><input id="__micad_btn_4" type="radio" name="stage" value="primates" /><label for="__micad_btn_4">Non-human primates</label><input id="__micad_btn_5" type="radio" name="stage" value="humans" /><label for="__micad_btn_5">Humans</label><input id="__micad_btn_6" type="radio" name="stage" value="any" checked="checked" /><label for="__micad_btn_6">Any</label></div></form><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmGo" method="get" action="javascript:alert('frmGo:_@action_was_not_set')" id="frmGo"><input name="term" value="." type="hidden" /></form></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=2541698" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=2541698" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div 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/21882402" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (111)In-Labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-d-Tyr-d-Lys(HSG)-d-Glu-d-Lys(HSG)-NH(2) (IMP-288).</a><span 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2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21834179" ref="ordinalpos=1&linkpos=3&log$=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 Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH(2) (IMP-156).</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 Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH(2) (IMP-156).<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/21834182" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (125)I-Labeled anti-mucin 1 bispecific antibody bsPAM4.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (125)I-Labeled anti-mucin 1 bispecific antibody bsPAM4.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Chopra A. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21834181" ref="ordinalpos=1&linkpos=5&log$=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> (99m)Tc-Ac-Lys(DTPA)-Tyr-Lys(DTPA)-Lys(thiosemicarbazonyl-glyoxyl-cysteinyl-)-NH2 (IMP-192).</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> (99m)Tc-Ac-Lys(DTPA)-Tyr-Lys(DTPA)-Lys(thiosemicarbazonyl-glyoxyl-cysteinyl-)-NH2 (IMP-192).<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 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