nih-gov/www.ncbi.nlm.nih.gov/books/n/micad/ECHGSETR199mTc/index.html?report=reader
2025-03-17 02:05:34 +00:00

128 lines
39 KiB
Text

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
<head>
<!-- For pinger, set start time and add meta elements. -->
<script type="text/javascript">var ncbi_startTime = new Date();</script>
<!-- Logger begin -->
<meta name="ncbi_db" content="books">
<meta name="ncbi_pdid" content="book-part">
<meta name="ncbi_acc" content="NBK23194">
<meta name="ncbi_domain" content="micad">
<meta name="ncbi_report" content="reader">
<meta name="ncbi_type" content="fulltext">
<meta name="ncbi_objectid" content="">
<meta name="ncbi_pcid" content="/NBK23194/?report=reader">
<meta name="ncbi_pagename" content="99mTc-Labeled mapatumumab - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf">
<meta name="ncbi_bookparttype" content="chapter">
<meta name="ncbi_app" content="bookshelf">
<!-- Logger end -->
<!--component id="Page" label="meta"/-->
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>99mTc-Labeled mapatumumab - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
<meta charset="utf-8">
<meta name="apple-mobile-web-app-capable" content="no">
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
<meta name="jr-col-layout" content="auto">
<meta name="jr-prev-unit" content="/books/n/micad/Tc99m-DCM20/?report=reader">
<meta name="jr-next-unit" content="/books/n/micad/MAG3-HBP99mTc/?report=reader">
<meta name="bk-toc-url" content="/books/n/micad/?report=toc">
<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="99mTc-Labeled mapatumumab">
<meta name="citation_publisher" content="National Center for Biotechnology Information (US)">
<meta name="citation_date" content="2009/05/20">
<meta name="citation_author" content="Arvind Chopra">
<meta name="citation_pmid" content="20641397">
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK23194/">
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
<meta name="DC.Title" content="99mTc-Labeled mapatumumab">
<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="2009/05/20">
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK23194/">
<meta name="description" content="Although anti-growth factor antibodies (Abs) are available for the treatment of cancers (1-3), another technique under investigation to treat this disease is the use of tumor necrosis factor&ndash;related apoptosis-inducing ligand (TRAIL) receptor (TRAIL-R) agonist Abs such as mapatumumab and lexatumumab (4, 5). These antibodies (Abs) activate a complex apoptotic pathway in the tumor cell, thereby inducing cell death.The apoptotic pathway and the four TRAIL-R types in humans (designated 1 through 4) have been described in detail by Johnstone et al. (4) and Ashkenazi (5). Mapatumumab (TRM-1 or HGS-ETR1) is a TRAIL-R1 monoclonal antibody (mAb) that targets TRAIL-R1; it is under commercial development and has been approved for clinical trials by the United States Food and Drug Administration (USFDA) to treat various cancers. A similar mAb, lexatumumab (TRM-2 or HGS-ETR2), is a TRAIL-R2 mAb that acts as an agonist specifically for the TRAIL-R2 and has been approved by the USFDA for clinical trials.">
<meta name="og:title" content="99mTc-Labeled mapatumumab">
<meta name="og:type" content="book">
<meta name="og:description" content="Although anti-growth factor antibodies (Abs) are available for the treatment of cancers (1-3), another technique under investigation to treat this disease is the use of tumor necrosis factor&ndash;related apoptosis-inducing ligand (TRAIL) receptor (TRAIL-R) agonist Abs such as mapatumumab and lexatumumab (4, 5). These antibodies (Abs) activate a complex apoptotic pathway in the tumor cell, thereby inducing cell death.The apoptotic pathway and the four TRAIL-R types in humans (designated 1 through 4) have been described in detail by Johnstone et al. (4) and Ashkenazi (5). Mapatumumab (TRM-1 or HGS-ETR1) is a TRAIL-R1 monoclonal antibody (mAb) that targets TRAIL-R1; it is under commercial development and has been approved for clinical trials by the United States Food and Drug Administration (USFDA) to treat various cancers. A similar mAb, lexatumumab (TRM-2 or HGS-ETR2), is a TRAIL-R2 mAb that acts as an agonist specifically for the TRAIL-R2 and has been approved by the USFDA for clinical trials.">
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK23194/">
<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/ECHGSETR199mTc/?report=reader">
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK23194/">
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&amp;subset=latin" rel="stylesheet" type="text/css">
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
<meta name="format-detection" content="telephone=no">
<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">
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
<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>
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
<meta name="ncbi_phid" content="CE8B22927D64E23100000000000C000A.m_5">
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
<body>
<!-- Book content! -->
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK23194/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
<style type="text/css">.st0{fill:#939598;}</style>
<g>
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
</g>
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/micad/Tc99m-DCM20/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">99mTc-Labeled mapatumumab</div><div class="j">Molecular Imaging and Contrast Agent Database (MICAD) [Internet]</div></div><div class="tail"><a href="/books/n/micad/MAG3-HBP99mTc/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK23194/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK23194/&amp;text=99mTc-Labeled%20mapatumumab"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/micad/?report=reader">Title Information</a><a href="/books/n/micad/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK23194/?report=classic">Switch to classic view</a><a href="/books/NBK23194/pdf/Bookshelf_NBK23194.pdf">PDF (125K)</a><a href="/books/NBK23194/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK23194%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8B22927D64E23100000000000C000A.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">&#10008;</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">&#10008;</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">&#9664;</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">&#9654;</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK23194_"><span class="title" itemprop="name"><sup>99m</sup>Tc-Labeled mapatumumab</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>99m</sup>Tc-EC-HGS-ETR1</div><p class="contribs">Chopra A.</p><p class="fm-aai"><a href="#_NBK23194_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figECHGSETR199mTcT1"><a href="/books/NBK23194/table/ECHGSETR199mTc.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobECHGSETR199mTcT1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="ECHGSETR199mTc.T1"><a href="/books/NBK23194/table/ECHGSETR199mTc.T1/?report=objectonly" target="object" rid-ob="figobECHGSETR199mTcT1">Table</a></h4><p class="float-caption no_bottom_margin">
<i>In vitro</i>
Rodents
</p></div></div><div id="ECHGSETR199mTc.Background"><h2 id="_ECHGSETR199mTc_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=99mTc+EC+HGS+ETR1" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Although anti-growth factor antibodies (Abs) are available for the treatment of cancers (<a class="bibr" href="#ECHGSETR199mTc.REF.1" rid="ECHGSETR199mTc.REF.1 ECHGSETR199mTc.REF.2 ECHGSETR199mTc.REF.3">1-3</a>), another technique under investigation to treat this disease is the use of tumor necrosis factor&#x02013;related apoptosis-inducing ligand (TRAIL) receptor (TRAIL-R) agonist Abs such as mapatumumab and lexatumumab (<a class="bibr" href="#ECHGSETR199mTc.REF.4" rid="ECHGSETR199mTc.REF.4 ECHGSETR199mTc.REF.5">4, 5</a>). These antibodies (Abs) activate a complex apoptotic pathway in the tumor cell, thereby inducing cell death.The apoptotic pathway and the four TRAIL-R types in humans (designated 1 through 4) have been described in detail by Johnstone et al. (<a class="bibr" href="#ECHGSETR199mTc.REF.4" rid="ECHGSETR199mTc.REF.4">4</a>) and Ashkenazi (<a class="bibr" href="#ECHGSETR199mTc.REF.5" rid="ECHGSETR199mTc.REF.5">5</a>). Mapatumumab (TRM-1 or HGS-ETR1) is a TRAIL-R1 monoclonal antibody (mAb) that targets TRAIL-R1; it is under commercial development and has been approved for <a href="http://clinicaltrials.gov/ct2/results?term=Mapatumumab" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">clinical trials</a> by the United States Food and Drug Administration (USFDA) to treat various cancers. A similar mAb, lexatumumab (TRM-2 or HGS-ETR2), is a TRAIL-R2 mAb that acts as an agonist specifically for the TRAIL-R2 and has been approved by the USFDA for <a href="http://clinicaltrials.gov/ct2/results?term=lexatumumab" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">clinical trials</a>.</p><p>Paclitaxel and docetaxel are anti-cancer drugs that inhibit the mitosis and proliferation of cells by interfering with the depolymerization of microtubules. The mechanism of action of these drugs was discussed in detail by Saloustros et al. (<a class="bibr" href="#ECHGSETR199mTc.REF.6" rid="ECHGSETR199mTc.REF.6">6</a>). Gong et al. observed that the anti-tumor activity of HGS-ETR1 could be enhanced in mice bearing colorectal cancer cell xenograft tumors with pretreatment with paclitaxel (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>). Using HGS-ETR1 labeled with radioactive technetium (<sup>99m</sup>Tc) (<sup>99m</sup>Tc-EC-HGS-ETR1), the investigators determined that the activity of HGS-ETR1 was increased because the pretreatment with paclitaxel upregulated the expression of TRAIL-R1 in Colo205 cell xenograft tumors in nude mice.</p></div><div id="ECHGSETR199mTc.Synthesis"><h2 id="_ECHGSETR199mTc_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20synthesis" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>The synthesis of <sup>99m</sup>Tc-EC-HGS-ETR1 was described by Gong et. al. (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>). Briefly, ethylenedicysteine (EC) was coupled to HGS-ETR1 for the chelation of <sup>99m</sup>Tc using sulfo-<i>N</i>-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) as the coupling agents. To do this, EC, NHS, and EDC were mixed with HGS-ETR1 and incubated for 17 h at room temperature. The product, EC-HGS-ETR1, was dialyzed (buffer not described) to remove any unbound reagents. The purification, the number of EC per HGS-ETR1, and the yield of EC-HGS-ETR1 were not described by the investigators. Labeling of EC-HGS-ETR1, to obtain <sup>99m</sup>Tc-EC-HGS-ETR1, was performed by adding sodium pertechnetate (<sup>99m</sup>TcO<sub>4</sub><sup>-</sup>) to a solution of EC mAb in the presence of tin chloride. The purification and yield of the radiolabeled product were not reported. Although the radiochemical purity of <sup>99m</sup>Tc-EC-HGS-ETR1 was reported to be &#x0003e;95% (determined with radio thin-layer chromatography), the specific activity of the labeled mAb was not reported.</p><p>For use as controls during scintigraphic imaging, <sup>99m</sup>Tc-EC-bovine serum albumin (BSA) and <sup>99m</sup>Tc-EC-isotype control mAb were also generated as described above (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>).</p></div><div id="ECHGSETR199mTc.In_Vitro_Studies_Tes"><h2 id="_ECHGSETR199mTc_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=99mTc+EC+HGS+ETR1+in+vitro" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>The steady state levels of TRAIL-R1 and TRAIL-R2 were determined in Colo205 (a human colorectal cancer tumor cell line) and PA-1 (a human ovarian cancer cell line) cells using immunoblots and fluorescence-activated cell sorting (FACS) (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>). Both receptor types were expressed in the two cell lines as determined with the immunoblots, but the levels were reported to be higher in the Colo205 cells than in the PA-1 cells. Similar results were obtained with FACS analysis of the two cell lines.</p><p>The concentration for 50% inhibition of cell proliferation (IC<sub>50</sub>) for Colo205 cells was determined to be 800 ng/mL and 150 ng/mL for HGS-ETR1 and HGS-ETR2, respectively (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>). The PA-1 cells were reported to be resistant to inhibition by both the Abs even at a concentration of 800 ng/mL. This indicated that the number of TRAIL-R1 and -R2 on the cell surface was too low to initiate apoptosis on binding of the two respective agonist TRAIL-R mAbs.</p></div><div id="ECHGSETR199mTc.Animal_Studies"><h2 id="_ECHGSETR199mTc_Animal_Studies_">Animal Studies</h2><div id="ECHGSETR199mTc.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=99mTc+EC+HGS+ETR1+rodentia" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Gong et al. studied the tumor uptake of <sup>99m</sup>Tc-EC-HGS-ETR1 in nude mice bearing Colo205 xenograft tumors (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>). Imaging studies were performed 12 days after inoculation with the cells when the tumor diameter was ~1 cm. The animals (4 or 5 mice/group) were intravenously (IV) injected with either <sup>99m</sup>Tc-EC-HGS-ETR1, <sup>99m</sup>Tc-EC-BSA, or the <sup>99m</sup>Tc-EC-isotype control mAb, and scintigraphic images were obtained 2, 24, and 48 h later. Using computer-outlined regions of interest, the counts per pixel of the tumor site and the normal muscle were used to obtain the tumor/muscle count density ratios (TM ratio). At 2 h after administration of the radiochemicals, little difference in the TM ratios was noted between the controls and the <sup>99m</sup>Tc-EC-HGS-ETR1&#x02013;treated animals. However, at 24 and 48 h after the injection of radioactivity, the TM ratios for the <sup>99m</sup>Tc-EC-HGS-ETR1 and the labeled control-injected animals was reported to be ~3 and ~2, respectively. No blocking studies were reported.</p><p>In another study, the Colo205 cell xenograft tumor&#x02013;bearing animals (<i>n</i> = 3 mice) were imaged before and after (at 2 and 24 h after an IV injection of <sup>99m</sup>Tc-EC-HGS-ETR1) treatment with paclitaxel (<a class="bibr" href="#ECHGSETR199mTc.REF.7" rid="ECHGSETR199mTc.REF.7">7</a>). Animals treated with paclitaxel were imaged 24 h after administration of the drug. When imaging was performed at 2 h after treatment with the labeled mAb, little difference in the TM ratio (~2) was noted in the tumors with or without the paclitaxel treatment. By 24 h the TM ratio was reported to have increased to ~4.2 in tumors of mice treated with paclitaxel compared with a TM ratio of ~2 in the untreated mice. In the same study, PA-1 cell xenograft tumors in animals (<i>n</i> = 3 mice) showed little change in the TM ratio (~1.5) both at 2 and 24 h after the <sup>99m</sup>Tc-EC-HGS-ETR1 injection. This indicated that very little of the labeled mAb bound to the tumors derived from the PA-1 cells.</p></div><div id="ECHGSETR199mTc.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=99mTc+EC+HGS+ETR1+Non+Primate+Mammals" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="ECHGSETR199mTc.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=99mTc+EC+HGS+ETR1+Non+Human+Primates" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div></div><div id="ECHGSETR199mTc.Human_Studies"><h2 id="_ECHGSETR199mTc_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&#x00026;Cmd=DetailsSearch&#x00026;Term=99mTc+EC+HGS+ETR1+Human+Studies" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No references are currently available.</p></div><div id="ECHGSETR199mTc.Supplemental_Informa"><h2 id="_ECHGSETR199mTc_Supplemental_Informa_">Supplemental Information</h2><p>[<a href="/books/n/micad/disclaimer/?report=reader">Disclaimers</a>]</p></div><div id="ECHGSETR199mTc.References"><h2 id="_ECHGSETR199mTc_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.1">Chase J.L. Clinical use of anti-vascular endothelial growth factor monoclonal antibodies in metastatic colorectal cancer. <span><span class="ref-journal">Pharmacotherapy. </span>2008;<span class="ref-vol">28</span>(11 Pt 2):23S&ndash;30S.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18980549" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18980549</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.2">Patel D.K. Clinical use of anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer. <span><span class="ref-journal">Pharmacotherapy. </span>2008;<span class="ref-vol">28</span>(11 Pt 2):31S&ndash;41S.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18980550" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18980550</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.3">Sachdev D., Singh R., Fujita-Yamaguchi Y., Yee D. Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer. <span><span class="ref-journal">Cancer Res. </span>2006;<span class="ref-vol">66</span>(4):2391&ndash;402.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16489046" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 16489046</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.4">Johnstone R.W., Frew A.J., Smyth M.J. The TRAIL apoptotic pathway in cancer onset, progression and therapy. <span><span class="ref-journal">Nat Rev Cancer. </span>2008;<span class="ref-vol">8</span>(10):782&ndash;98.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18813321" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18813321</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.5">Ashkenazi A. Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. <span><span class="ref-journal">Nat Rev Drug Discov. </span>2008;<span class="ref-vol">7</span>(12):1001&ndash;12.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18989337" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18989337</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.6">Saloustros E., Mavroudis D., Georgoulias V. Paclitaxel and docetaxel in the treatment of breast cancer. <span><span class="ref-journal">Expert Opin Pharmacother. </span>2008;<span class="ref-vol">9</span>(15):2603&ndash;16.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18803448" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18803448</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="ECHGSETR199mTc.REF.7">Gong J., Yang D., Kohanim S., Humphreys R., Broemeling L., Kurzrock R. Novel in vivo imaging shows up-regulation of death receptors by paclitaxel and correlates with enhanced antitumor effects of receptor agonist antibodies. <span><span class="ref-journal">Mol Cancer Ther. </span>2006;<span class="ref-vol">5</span>(12):2991&ndash;3000.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17148761" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 17148761</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK23194_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Arvind Chopra</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, NIH, Bethesda, MD 20894<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@dacim" class="oemail">vog.hin.mln.ibcn@dacim</a></div></div></div><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">March 16, 2009</span>; Last Update: <span itemprop="dateModified">May 20, 2009</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&amp;targetsite=external&amp;targetcat=link&amp;targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Chopra A. 99mTc-Labeled mapatumumab. 2009 Mar 16 [Updated 2009 May 20]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/micad/Tc99m-DCM20/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/micad/MAG3-HBP99mTc/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobECHGSETR199mTcT1"><div id="ECHGSETR199mTc.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23194/table/ECHGSETR199mTc.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ECHGSETR199mTc.T1_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Chemical name:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-Labeled mapatumumab<br /></td><td rowspan="9" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Abbreviated name:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-EC-HGS-ETR1<br /></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Synonym:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Agent Category:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antibody</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Target:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tumor necrosis factor&#x02013;related apoptosis-inducing ligand receptor 1 (TRAIL-R1)<br /></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Target Category:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Receptor</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Method of detection:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Single-photon emission computed tomography (SPECT); gamma planar imaging</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Source of signal / contrast:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Activation:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Studies:</b>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
<ul class="simple-list"><li class="half_rhythm"><div>
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" />
<i>In vitro</i>
</div></li><li class="half_rhythm"><div>
<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
</div></li></ul>
</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Click here for the <a href="/sites/entrez?Db=gene&#x00026;Cmd=retrieve&#x00026;dopt=full_report&#x00026;list_uids=8743&#x00026;log$=databasead&#x00026;logdbfrom=protein#refseq" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">nucleotice, protein and gene</a> information regarding TRAIL receptors.</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
<!-- Book content -->
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal104 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
</html>