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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>99mTc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="citation_title" content="99mTc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody">
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<meta name="citation_date" content="2008/01/28">
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<meta name="citation_author" content="Kenneth T. Cheng">
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<meta name="DC.Contributor" content="Kenneth T. Cheng">
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<meta name="og:description" content="99mTc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody (99mTc-HYNIC-CC49 sc(Fv)2 MAb), which is formed by the conjugation of 99mTc with a bioengineered anti–tumor-associated glycoprotein 72 (TAG-72) antibody construct, has been developed for single-photon emission computed tomography (SPECT) imaging of cancers that express TAG-72 (1). 99mTc is a gamma emitter with a half-life (t½) of 6.02 h.">
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id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK23432_"><span class="title" itemprop="name"><sup>99m</sup>Tc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody </span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb</div><p class="contribs">Cheng KT.</p><p class="fm-aai"><a href="#_NBK23432_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="figCC49ScFv2Tc99mT1"><a href="/books/NBK23432/table/CC49ScFv2Tc99m.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCC49ScFv2Tc99mT1"><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="CC49ScFv2Tc99m.T1"><a href="/books/NBK23432/table/CC49ScFv2Tc99m.T1/?report=objectonly" target="object" rid-ob="figobCC49ScFv2Tc99mT1">Table</a></h4><p class="float-caption no_bottom_margin">
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</p></div></div><div id="CC49ScFv2Tc99m.Background"><h2 id="_CC49ScFv2Tc99m_Background_">Background</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p><sup>99m</sup>Tc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody (<sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb), which is formed by the conjugation of <sup>99m</sup>Tc with a bioengineered anti–tumor-associated glycoprotein 72 (TAG-72) antibody construct, has been developed for single-photon emission computed tomography (SPECT) imaging of cancers that express TAG-72 (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>). <sup>99m</sup>Tc is a gamma emitter with a half-life (<i>t</i><sub>½</sub>) of 6.02 h.</p><p>The TAG-72 antigen was isolated from the LS-174T human colon cancer xenograft as a high molecular weight glycoprotein (molecular mass of 10<sup>6</sup> Da) with mucin-like characteristics (<a href="#CC49ScFv2Tc99m.REF.2">2-5</a>). It is expressed on a variety of human adenocarcinomas such as pancreatic, breast, colorectal, prostate, endometrial, and ovarian cancers. This antigen has also been shown to be shed into the serum of cancer patients (<a class="bibr" href="#CC49ScFv2Tc99m.REF.6" rid="CC49ScFv2Tc99m.REF.6">6</a>). The murine MAb B72.3 against TAG-72 was initially generated by immunization of mice with a membrane-enriched fraction of a human breast carcinoma (<a class="bibr" href="#CC49ScFv2Tc99m.REF.7" rid="CC49ScFv2Tc99m.REF.7">7</a>). With use of affinity-purified TAG-72 from LS-174T as an immunogen, CC49 and other anti–TAG-2 MAbs with higher affinity constants (<i>K</i><sub>a</sub>) have been produced and characterized (<a href="#CC49ScFv2Tc99m.REF.1">1-3</a>, <a class="bibr" href="#CC49ScFv2Tc99m.REF.7" rid="CC49ScFv2Tc99m.REF.7">7</a>).</p><p>Radiolabeled MAbs have been developed for both the diagnosis and treatment of tumors (<a class="bibr" href="#CC49ScFv2Tc99m.REF.8" rid="CC49ScFv2Tc99m.REF.8">8</a>). Radiolabeled B72.3 and CC49 have shown excellent tumor localization capabilities with potential diagnostic and therapeutic applications in the clinical setting (<a class="bibr" href="#CC49ScFv2Tc99m.REF.9" rid="CC49ScFv2Tc99m.REF.9">9</a>, <a class="bibr" href="#CC49ScFv2Tc99m.REF.10" rid="CC49ScFv2Tc99m.REF.10">10</a>). Because of their relatively large size, radiolabeled intact MAbs tend to have unfavorable imaging kinetics, poor tumor penetration, and high potential for human anti-mouse antibody response (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>, <a href="#CC49ScFv2Tc99m.REF.11">11-13</a>). One approach to minimize these problems is reducing intact antibodies to antibody fragments such as F(ab’)<sub>2</sub> and Fab’ (<a class="bibr" href="#CC49ScFv2Tc99m.REF.14" rid="CC49ScFv2Tc99m.REF.14">14</a>). Another approach is the development of genetic engineering methods to obtain single-chain Fv constructs (scFv) and multivalent scFv constructs (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>, <a class="bibr" href="#CC49ScFv2Tc99m.REF.15" rid="CC49ScFv2Tc99m.REF.15">15</a>, <a class="bibr" href="#CC49ScFv2Tc99m.REF.16" rid="CC49ScFv2Tc99m.REF.16">16</a>). These scFv constructs contain the variable regions of the light chain (V<sub>L</sub>) and heavy chain (V<sub>H</sub>) connected by a flexible linker. Colcher et al. (<a class="bibr" href="#CC49ScFv2Tc99m.REF.17" rid="CC49ScFv2Tc99m.REF.17">17</a>) constructed the monomeric CC49 scFv MAb (~27 kDa), which selectively recognizes a unique sialyl-Tn epitope of TAG-72. The radioiodinated CC49 scFv appeared to clear rapidly from the blood with good tumor penetration (<a class="bibr" href="#CC49ScFv2Tc99m.REF.16" rid="CC49ScFv2Tc99m.REF.16">16</a>, <a class="bibr" href="#CC49ScFv2Tc99m.REF.18" rid="CC49ScFv2Tc99m.REF.18">18</a>). To further improve the imaging kinetics, Pavlinkova et al. (<a class="bibr" href="#CC49ScFv2Tc99m.REF.18" rid="CC49ScFv2Tc99m.REF.18">18</a>) constructed the high-affinity dimer CC49 sc(Fv)<sub>2</sub> (~60 kDa). The radioiodinated CC49 sc(Fv)<sub>2</sub> showed good stability and increased avidity <i>in vivo</i> compared with the radioiodinated CC49 scFv construct.</p><p>With direct or indirect labeling, MAbs can be labeled with <sup>99m</sup>Tc, a gamma emitter with ideal SPECT imaging properties. Direct labeling involves reduction of <sup>99m</sup>Tc-pertechnetate and nonspecific binding of the reduced <sup>99m</sup>Tc to donor atoms, namely thiol, amide, amino, and carboxylate (<a class="bibr" href="#CC49ScFv2Tc99m.REF.19" rid="CC49ScFv2Tc99m.REF.19">19</a>). Indirect labeling uses a bifunctional chelating agent, which can be more binding site–specific on the MAb molecule. Goel et al. (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>) used hydrazinonicotinamide (HYNIC) as a bifunctional coupling agent to label CC49 sc(Fv)<sub>2</sub> with <sup>99m</sup>Tc. The <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb showed good tumor targeting and <i>in vivo</i> biodistribution properties.</p></div><div id="CC49ScFv2Tc99m.Synthesis"><h2 id="_CC49ScFv2Tc99m_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Goel et al. (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>) reported the construction and radiolabeling of the <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb. The CC49 scFv (V<sub>L</sub>-linker-V<sub>H</sub>) was derived from the murine MAb CC49 cloned in the yeast expression vector pPICZαA and constructed with the 205C linker. The bacterial scFv construct was used as the template DNA for the expression of the scFv in competent <i>P. pastoris</i> KM71 cells. The construction of the divalent sc(Fv)<sub>2</sub> (V<sub>L</sub>-linker-V<sub>H</sub>-linker-V<sub>L</sub>-linker-V<sub>H</sub>-His<sub>6</sub>) was performed as described by Goel et al. (<a class="bibr" href="#CC49ScFv2Tc99m.REF.20" rid="CC49ScFv2Tc99m.REF.20">20</a>) using the 205C linker in a <i>P. pastoris</i> expression system, and the final construct was purified from the secreted medium with immobilized metal affinity chromatography. The preparation was shown to be >95% pure by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size-exclusion high-performance liquid chromatography (HPLC) showed the molecular mass to be 60 kDa. Competitive solid-phase competition enzyme-linked immunosorbent assay (ELISA) with bovine submaxillary gland mucin (BSM) confirmed the immunoreactivity of the divalent construct. To radiolabel the agent, the hydrazino-modification of CC49 sc(Fv)<sub>2</sub> was achieved by reacting the construct with the <i>N</i>-hydroxysuccinimide ester of succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH) at a molar ratio of 10:1 in sodium phosphate buffer (pH 7.8). It was estimated that there were ~2.3 SHNH groups per sc(Fv)<sub>2</sub>. In the radiolabeling procedure, sodium <sup>99m</sup>Tc-pertechnetate, tricine, and stannous chloride were first mixed, then SHNH-derivatized CC49 sc(Fv)<sub>2</sub> was added, and the reaction mixture was incubated at room temperature for 45 min. The final <sup>99m</sup>Tc-HYNIC-CC49 sc(FV)<sub>2</sub> MAb was purified on a Sephadex G-25 column. The specific activity was 74–111 MBq/mg (2–3 mCi/mg) or 4.44–6.66 MBq/nmol (0.12–0.18 mCi/nmol) on the basis of the estimated 60-kDa molecular weight) with a radiochemical purity ≥95% (HPLC analysis). On SDS-PAGE, >90% of the total radioactivity was associated with the protein band of 58 kDa.</p></div><div id="CC49ScFv2Tc99m.In_Vitro_Studies_Tes"><h2 id="_CC49ScFv2Tc99m_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The immunoreactivity of <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb by solid-phase ELISA with immobilized BSM was 85–95% with a nonspecific binding of 0.8–1.5% (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>).</p><p><i>In vitro</i> stability studies of <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb were conducted by incubating the radiolabeled MAb construct in 1% bovine serum albumin (BSA) or 1% mouse serum at 37ºC for 24 h (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>). By HPLC analysis, <20% loss of <sup>99m</sup>Tc label was detected in 1% BSA. In the 1% mouse serum, ~20% and 10% of the <sup>99m</sup>Tc were associated with low molecular weight proteins (<50 kDa) and high molecular weight proteins (>130 kDa), respectively. This latter protein fraction suggested the possibility of aggregation of the radiolabel with serum proteins.</p><p>Using the Scatchard plot and surface plasmon resonance technique to measure the real-time interactions, Goel et al. (<a class="bibr" href="#CC49ScFv2Tc99m.REF.21" rid="CC49ScFv2Tc99m.REF.21">21</a>) reported the <i>K</i><sub>a</sub> of unlabeled CC49 sc(Fv)<sub>2</sub> to be 2.75 × 10<sup>7</sup> M−<sup>1</sup> in binding to the immobilized BSM. In comparison, the <i>K</i><sub>a</sub> for the intact CC49 MAb construct was 1.14 × 10<sup>8</sup> M−<sup>1</sup>.</p></div><div id="CC49ScFv2Tc99m.Animal_Studies"><h2 id="_CC49ScFv2Tc99m_Animal_Studies_">Animal Studies</h2><div id="CC49ScFv2Tc99m.Rodents"><h3>Rodents</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Biodistribution studies of <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb were performed in nude mice bearing LS-147T s.c. human colon carcinomas (~250–300 mm<sup>3</sup>) (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>). Each mouse received 0.37 MBq (10 μCi) of <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> mAb by i.v. administration. The blood elimination <i>t</i><sub>½</sub> was 144 min, and the whole-body clearance <i>t</i><sub>½</sub> was 184 ± 19 min (<i>n</i> = 3). The radioactivity levels (<i>n</i> = 3 × 2) in percentage injected dose per gram (% ID/g) of the tumors were 9.9 ± 0.7 (0.5 h), 10.9 ± 0.8 (1 h), 12.6 ± 0.4 (4 h), 7.2 ± 0.7 (8 h), 2.3 ± 0.1 (16 h), and 1.2 ± 0.0 (24 h). At 16 h, the tumor/blood ratio was 4.6:1. At 0.5 h, the radioactivity levels (% ID/g) of major organs were 13.9 ± 1.1 (blood), 18.9 ± 1.5 (liver), 13.4 ± 1.2 (spleen), 33.9 ± 1.8 (kidneys), and 5.4 ± 0.8 (lungs). At 4 h, these levels changed to 4.3 ± 0.2 (blood), 14.8 ± 1.3 (liver), 9.7 ± 0.7 (spleen), 27.3 ± 1.4 (kidneys), and 1.3 ± 0.0 (lungs). By 24 h, these levels declined to 0.1 ± 0.0 (blood), 1.2 ± 0.0 (liver), 1.0 ± 0.0 (spleen), 2.4 ± 0.3 (kidneys), and 0.0 ± 0.0 (lungs). Macroautoradiography studies performed in mice at 6 h and 16 h after radioactivity administration confirmed a high degree of tumor localization and negligible retention in the blood and normal organs (<a class="bibr" href="#CC49ScFv2Tc99m.REF.1" rid="CC49ScFv2Tc99m.REF.1">1</a>). The exceptions were the liver and pancreas, but the tumor radioactivity levels were still two-fold higher at both 6 and 16 h in these two organs. The tumor remained positive at 16 h after injection. The study suggested that <sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb probably underwent hepatobiliary excretion.</p></div><div id="CC49ScFv2Tc99m.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22%20SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20%28dog%20OR%20rabbit%20OR%20pig%20OR%20sheep%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="CC49ScFv2Tc99m.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20%28primate%20NOT%20human%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="CC49ScFv2Tc99m.Human_Studies"><h2 id="_CC49ScFv2Tc99m_Human_Studies_">Human Studies</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=%22SUBSTANCENAME%22%5BSubstance%20Name%5D%20AND%20human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="CC49ScFv2Tc99m.references"><h2 id="_CC49ScFv2Tc99m_references_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.1">Goel A. , Baranowska-Kortylewicz J. , Hinrichs S.H. , Wisecarver J. , Pavlinkova G. , Augustine S. , Colcher D. , Booth B.J. , Batra S.K. 99mTc-labeled divalent and tetravalent CC49 single-chain Fv's: novel imaging agents for rapid in vivo localization of human colon carcinoma. <span><span class="ref-journal">J Nucl Med. </span>2001;<span class="ref-vol">
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<strong>42</strong>
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</span>(10):1519–27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11585867" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11585867</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.2">Muraro R. , Kuroki M. , Wunderlich D. , Poole D.J. , Colcher D. , Thor A. , Greiner J.W. , Simpson J.F. , Molinolo A. , Noguchi P. et al. Generation and characterization of B72.3 second generation monoclonal antibodies reactive with the tumor-associated glycoprotein 72 antigen. <span><span class="ref-journal">Cancer Res. </span>1988;<span class="ref-vol">
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<strong>48</strong>
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</span>(16):4588–96.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3396010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3396010</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.3">Johnson V.G. , Schlom J. , Paterson A.J. , Bennett J. , Magnani J.L. , Colcher D. Analysis of a human tumor-associated glycoprotein (TAG-72) identified by monoclonal antibody B72.3. <span><span class="ref-journal">Cancer Res. </span>1986;<span class="ref-vol">
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<strong>46</strong>
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</span>(2):850–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3940648" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3940648</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.4">Katari R.S. , Fernsten P.D. , Schlom J. Characterization of the shed form of the human tumor-associated glycoprotein (TAG-72) from serous effusions of patients with different types of carcinomas. <span><span class="ref-journal">Cancer Res. </span>1990;<span class="ref-vol">
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<strong>50</strong>
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</span>(16):4885–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2379152" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2379152</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.5">Xiao J. , Horst S. , Hinkle G. , Cao X. , Kocak E. , Fang J. , Young D. , Khazaeli M. , Agnese D. , Sun D. , Martin E. Pharmacokinetics and clinical evaluation of 125I-radiolabeled humanized CC49 monoclonal antibody (HuCC49deltaC(H)2) in recurrent and metastatic colorectal cancer patients. <span><span class="ref-journal">Cancer Biother Radiopharm. </span>2005;<span class="ref-vol">
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<strong>20</strong>
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</span>(1):16–26.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15778575" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15778575</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.6">Paterson A.J. , Schlom J. , Sears H.F. , Bennett J. , Colcher D. A radioimmunoassay for the detection of a human tumor-associated glycoprotein (TAG-72) using monoclonal antibody B72.3. <span><span class="ref-journal">Int J Cancer. </span>1986;<span class="ref-vol">
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<strong>37</strong>
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</span>(5):659–66.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3699929" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3699929</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.7">Colcher D. , Hand P.H. , Nuti M. , Schlom J. A spectrum of monoclonal antibodies reactive with human mammary tumor cells. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>1981;<span class="ref-vol">
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</span>(5):3199–203.</span> [<a href="/pmc/articles/PMC319528/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC319528</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/6789331" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6789331</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.8">Kowalsky R.J. , Falen S.W. <span><span class="ref-journal">and Radiopharmaceuticals in nuclear pharmacy and nuclear medicine, American Pharmacists Association: Washington, D.C. p. 733-752. </span>2004</span></div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.9">Colcher D. , Minelli M.F. , Roselli M. , Muraro R. , Simpson-Milenic D. , Schlom J. Radioimmunolocalization of human carcinoma xenografts with B72.3 second generation monoclonal antibodies. <span><span class="ref-journal">Cancer Res. </span>1988;<span class="ref-vol">
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<strong>48</strong>
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</span>(16):4597–603.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3396011" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3396011</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.10">Colcher D. , Esteban J. , Carrasquillo J.A. , Sugarbaker P. , Reynolds J.C. , Bryant G. , Larson S.M. , Schlom J. Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72.3) in patients with carcinoma. <span><span class="ref-journal">Cancer Res. </span>1987;<span class="ref-vol">
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<strong>47</strong>
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</span>(15):4218–24.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3607761" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3607761</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.11">Britton K.E. The development of new radiopharmaceuticals. <span><span class="ref-journal">Eur J Nucl Med. </span>1990;<span class="ref-vol">
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<strong>16</strong>
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</span>(4-6):373–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2190837" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2190837</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.12">Jain R.K. Transport of molecules across tumor vasculature. <span><span class="ref-journal">Cancer Metastasis Rev. </span>1987;<span class="ref-vol">
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<strong>6</strong>
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</span>(4):559–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3327633" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3327633</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.13">Primus F.J. , Bennett S.J. , Kim E.E. , DeLand F.H. , Zahn M.C. , Goldenberg D.M. Circulating immune complexes in cancer patients receiving goat radiolocalizing antibodies to carcinoembryonic antigen. <span><span class="ref-journal">Cancer Res. </span>1980;<span class="ref-vol">
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<strong>40</strong>
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</span>(3):497–501.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7008935" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7008935</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.14">Behr T. , Becker W. , Hannappel E. , Goldenberg D.M. , Wolf F. <span class="ref-title">Targeting of liver metastases of colorectal cancer with IgG, F(ab')2, and Fab' anti-carcinoembryonic antigen antibodies labeled with 99mTc: the role of metabolism and kinetics </span><span class="ref-journal">Cancer Res</span> 1995<strong>55</strong>Suppl235777s–5785s. [<a href="https://pubmed.ncbi.nlm.nih.gov/7493346" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7493346</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.15">Bird R.E. , Hardman K.D. , Jacobson J.W. , Johnson S. , Kaufman B.M. , Lee S.M. , Lee T. , Pope S.H. , Riordan G.S. , Whitlow M. Single-chain antigen-binding proteins. <span><span class="ref-journal">Science. </span>1988;<span class="ref-vol">
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<strong>242</strong>
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</span>(4877):423–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3140379" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3140379</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.16">Colcher D. , Bird R. , Roselli M. , Hardman K.D. , Johnson S. , Pope S. , Dodd S.W. , Pantoliano M.W. , Milenic D.E. , Schlom J. In vivo tumor targeting of a recombinant single-chain antigen-binding protein. <span><span class="ref-journal">J Natl Cancer Inst. </span>1990;<span class="ref-vol">
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<strong>82</strong>
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</span>(14):1191–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2362290" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2362290</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.17">Colcher D. , Goel A. , Pavlinkova G. , Beresford G. , Booth B. , Batra S.K. Effects of genetic engineering on the pharmacokinetics of antibodies. <span><span class="ref-journal">Q J Nucl Med. </span>1999;<span class="ref-vol">
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<strong>43</strong>
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</span>(2):132–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10429508" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10429508</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.18">Pavlinkova G. , Beresford G.W. , Booth B.J. , Batra S.K. , Colcher D. Pharmacokinetics and biodistribution of engineered single-chain antibody constructs of MAb CC49 in colon carcinoma xenografts. <span><span class="ref-journal">J Nucl Med. </span>1999;<span class="ref-vol">
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<strong>40</strong>
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</span>(9):1536–46.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10492377" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10492377</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.19">Fritzberg A.R. , Berninger R.W. , Hadley S.W. , Wester D.W. Approaches to radiolabeling of antibodies for diagnosis and therapy of cancer. <span><span class="ref-journal">Pharm Res. </span>1988;<span class="ref-vol">
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<strong>5</strong>
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</span>(6):325–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3072555" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3072555</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.20">Goel A. , Beresford G.W. , Colcher D. , Pavlinkova G. , Booth B.J. , Baranowska-Kortylewicz J. , Batra S.K. Divalent forms of CC49 single-chain antibody constructs in Pichia pastoris: expression, purification, and characterization. <span><span class="ref-journal">J Biochem (Tokyo). </span>2000;<span class="ref-vol">
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<strong>127</strong>
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</span>(5):829–36.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10788792" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10788792</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="CC49ScFv2Tc99m.REF.21">Goel A. , Colcher D. , Baranowska-Kortylewicz J. , Augustine S. , Booth B.J. , Pavlinkova G. , Batra S.K. Genetically engineered tetravalent single-chain Fv of the pancarcinoma monoclonal antibody CC49: improved biodistribution and potential for therapeutic application. <span><span class="ref-journal">Cancer Res. </span>2000;<span class="ref-vol">
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<strong>60</strong>
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</span>(24):6964–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11156397" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11156397</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK23432_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Kenneth T. Cheng</span>, PhD<div class="affiliation small">
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National Center for Biotechnology Information, NLM, NIH, Bethesda, MD,
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<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@dacim" class="oemail">vog.hin.mln.ibcn@dacim</a>
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</div></div><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">June 19, 2007</span>; Last Update: <span itemprop="dateModified">January 28, 2008</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Cheng KT. 99mTc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody. 2007 Jun 19 [Updated 2008 Jan 28]. 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/Annexin-HYNIC-99mTc/?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/CC49ScFv4Tc99m/?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="figobCC49ScFv2Tc99mT1"><div id="CC49ScFv2Tc99m.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23432/table/CC49ScFv2Tc99m.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CC49ScFv2Tc99m.T1_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Chemical name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-Hydrazinonicotinamide-anti-TAG-72 CC49 divalent single-chain Fv monoclonal antibody</td><td rowspan="9" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Abbreviated name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-HYNIC-CC49 sc(Fv)<sub>2</sub> MAb</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Synonym:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>99m</sup>Tc-CC49 sc(Fv)<sub>2</sub> MAb, <sup>99m</sup>Tc-CC49 MAb</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;">Divalent single-chain Fv monoclonal antibody (sc(Fv)<sub>2</sub> MAb</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;">TAG-72</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;">Antibody to antigen binding</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Method of detection:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Single-photon emission computed tomography (SPECT), planar gamma 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>99m</sup>Tc</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></ul>
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<ul class="simple-list"><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
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</div></li></ul>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Click on <a href="/entrez/viewer.fcgi?db=protein&id=144964805" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?db=nuccore&id=21689921" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nucleotide</a> (RefSeq), and <a href="/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=182875&ordinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gene</a> for more information about TAG-72</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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