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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="#__NBK24582_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK24582_dtls__"><div>Bethesda (MD): <a href="https://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>; 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/TcTTA1/" title="Previous page in this title">&lt; Prev</a><a class="active page_link next" href="/books/n/micad/Z-MAG3-99mTc/" title="Next page in this title">Next &gt;</a></div></div></div></div></div>
<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK24582_"><span class="title" itemprop="name"><sup>99m</sup>Tc-Mercaptoacetyl-Glu-Glu-Glu-Affibody Z<sub>HER2:342</sub></span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub></div><p class="contrib-group"><span itemprop="author">Kam Leung</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK24582_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK24582_ai__"><div class="contrib half_rhythm"><span itemprop="author">Kam Leung</span>, PhD<div class="affiliation small">National Center for Biotechnology Information, NLM, NIH<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 class="small">Corresponding author.</div></div></div><p class="small">Created: <span itemprop="datePublished">March 16, 2008</span>; Last Update: <span itemprop="dateModified">April 7, 2008</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="Z-MaEEE-99mTc.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK24582/table/Z-MaEEE-99mTc.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Z-MaEEE-99mTc.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-Mercaptoacetyl-Glu-Glu-Glu-Affibody Z<sub>HER2:342</sub></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-MaEEE-Z<sub>HER2:342</sub></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 fragment, Affibody</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;">EGF HER2 receptor</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;">SPECT, gamma planar</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
<b>Source of signal:</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;">
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<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 on <a href="/entrez/viewer.fcgi?db=protein&#x00026;val=54792098" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?val=NM_201282.1" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">nucleotide</a> (RefSeq), and <a href="/entrez/query.fcgi?db=gene&#x00026;cmd=Retrieve&#x00026;dopt=Graphics&#x00026;list_uids=1956" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">gene</a> for more information about HER2.</td></tr></tbody></table></div></div><div id="Z-MaEEE-99mTc.Background"><h2 id="_Z-MaEEE-99mTc_Background_">Background</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Epidermal growth factor (EGF) is a cytokine that comprises 53 amino acids (6.2 kDa) and is secreted by ectodermic cells, monocytes, kidneys, and duodenal glands (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.1">1</a>). EGF stimulates growth of epidermal and epithelial cells. EGF and at least seven other growth factors and their transmembrane receptor kinases play important roles in cell proliferation, survival, adhesion, migration, and differentiation. The EGF receptor (EGFR) family consists of four transmembrane receptors: EGFR (HER1/erbB-1), HER2 (erbB-2/neu), HER3 (erbB-3), and HER4 (erbB-4) (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.2">2</a>). HER1, HER3, and HER4 comprise three major functional domains: an extracellular ligand-binding domain, a hydrophobic transmembrane domain, and a cytoplasmic tyrosine kinase domain. No ligand has been clearly identified for HER2. However, HER2 can be activated as a result of ligand binding to other HER receptors with the formation of receptor homodimers and/or heterodimers (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.3">3</a>). HER1 and HER2 are overexpressed on many solid tumor cells such as breast, non-small cell lung, head and neck, and colon cancers (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.4" data-bk-pop-others="Z-MaEEE-99mTc.REF.5 Z-MaEEE-99mTc.REF.6">4-6</a>). The high levels of HER1 and HER2 expression on cancer cells are associated with a poor prognosis (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.7" data-bk-pop-others="Z-MaEEE-99mTc.REF.8 Z-MaEEE-99mTc.REF.9 Z-MaEEE-99mTc.REF.10">7-10</a>).</p><p>Trastuzumab is a humanized IgG<sub>1</sub> monoclonal antibody (mAb) against the extracellular domain of recombinant HER2 with an affinity constant (<i>K</i><sub>d</sub>) of 0.1 nM (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.11">11</a>). Trastuzumab is approved for clinical use for anti-cancer therapies in both Europe and North America. <sup>111</sup>In-Trastuzumab, Cy5.5-trastuzumab, and <sup>68</sup>Ga-trastuzumab-F(ab')<sub>2</sub> eveloped for imaging human breast cancer (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.12" data-bk-pop-others="Z-MaEEE-99mTc.REF.13 Z-MaEEE-99mTc.REF.14 Z-MaEEE-99mTc.REF.15 Z-MaEEE-99mTc.REF.16">12-16</a>). However, the pharmacokinetics of the intact radiolabeled mAb, with high liver uptake and slow blood elimination, are generally not ideal for imaging. Smaller antibody fragments, such as Fab or F(ab&#x000b4;)<sub>2</sub>, have better imaging pharmacokinetics because they are rapidly excreted by the kidneys. A novel class of recombinant affinity ligands (Affibody molecules) for HER2 was constructed on the basis of the Z-domain residues (58 amino acids) from one of the IgG-binding domains of staphylococcal protein A (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.17">17</a>). Affibody molecules exhibit high binding affinity (<i>K</i><sub>d</sub>) to HER2 with <i>K</i><sub>d</sub> values &#x0003c;100 pM. Various radiolabeled Affibody molecules have been studied in terms of their ability to image HER2 in tumors [<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=affibody%20and%20HER2" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]. Mercaptoacetyl-Gly-Gly-Gly (MAG3) was used a chelating linker for coupling <sup>99m</sup>Tc to Z<sub>HER2:342</sub> Affibody (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.18">18</a>). <sup>99m</sup>Tc-MAG3-Z<sub>HER2:342</sub> has been evaluated in nude mice bearing human colon adenocarcinoma tumors, resulting in high tumor/blood and tumor/muscle ratios. However, <sup>99m</sup>Tc-MAG3-Z<sub>HER2:342</sub> exhibited a high hepatobiliary clearance, which resulted in a high radioactivity in the intestines at 4 h after injection (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.19">19</a>). Therefore, glutamic acid was used as the chelating linker to decrease the lipophilicity of Z<sub>HER2:342</sub> Affibody to suppress hepatobiliary clearance (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.20">20</a>). <sup>99m</sup>Tc-Mercaptoacetyl-Glu-Glu-Glu-Affibody Z<sub>HER2:342</sub> (<sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub>) was found to a have favorable biodistribution in nude mice bearing SKOV-3 tumors, resulting in a 3-fold lower hepatobiliary clearance than <sup>99m</sup>Tc-MAG3-Z<sub>HER2:342</sub>.</p></div><div id="Z-MaEEE-99mTc.Synthesis"><h2 id="_Z-MaEEE-99mTc_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20and%20synthesis" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Z<sub>HER2:342</sub> Affibody was prepared by standard solid phase peptide synthesis. MaEEE-Z<sub>HER2:342</sub> was prepared by addition of MaEEE to the N-terminal of the Z-Affibody (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.20">20</a>). <sup>99m</sup>Tc as pertechnetate was added to a solution of MaEEE-Z<sub>HER2:342</sub> containing SnCl<sub>2</sub>. The mixture was incubated for 60 min at room temperature. The labeling efficiency of <sup>99m</sup>Tc incorporation was 90 &#x000b1; 2% with &#x0003e;98% purity. <sup>99m</sup>Tc- MaEEE-Z<sub>HER2:342</sub> was purified by size-exclusion chromatography. Specific activities of the preparations were not reported. <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub> was found to be stable after incubation in murine blood plasma (&#x0003e;99%) at 37&#x000b0;C for 1 h or solution containing 300-fold excess cysteine (93 &#x000b1; 3%) at 37&#x000b0;C for 2 h.</p></div><div id="Z-MaEEE-99mTc.In_Vitro_Studies_Tes"><h2 id="_Z-MaEEE-99mTc_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20and%20in%20vitro" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Tran et al. (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.20">20</a>) performed binding experiments with MaEEE-Z<sub>HER2:342</sub> with use of a Biacore sensor chip immobilized with extracellular domain of HER2 protein. The <i>K</i><sub>d</sub> values were 410 and 80 pM for MaEEE-Z<sub>HER2:342</sub> and Z<sub>HER2:342</sub>, respectively. Hence, the binding affinity of the synthetic Affibody molecule MaEEE-Z<sub>HER2:342</sub> was 4.1-fold lower than the parent Affibody molecule Z<sub>HER2:342</sub>. <i>In vitro</i> binding specificity tests showed that binding of <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub> to SKOV-3 cells expressing HER2 was receptor-mediated because saturation of receptors by preincubation with non-labeled Z<sub>HER2:342</sub> significantly decreased binding of <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub>. The antigen binding capacity of <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub> was 67%. The cell-bound radioactivity remained constant at ~70% of the initially bound activity for up to 24 h when the cells were incubated with <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub>. In contrast, cells incubated with <sup>125</sup>I-Z<sub>HER2:342</sub> retained ~40% of the original cell-associated radioactivity.</p></div><div id="Z-MaEEE-99mTc.Animal_Studies"><h2 id="_Z-MaEEE-99mTc_Animal_Studies_">Animal Studies</h2><div id="Z-MaEEE-99mTc.Rodents"><h3>Rodents</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20and%20rodentia" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>Tran et al. (<a class="bk_pop" href="#Z-MaEEE-99mTc.REF.20">20</a>) performed biodistribution studies of 0.1 MBq (2.7 &#x003bc;Ci) <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub> in nude mice (<i>n</i> = 4) bearing SKOV-3 xenografts. <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub> (0.14 nmol) was injected s.c. to each mouse. The initial tracer accumulation in the SKOV-3 tumors was 9.1% injected dose per gram (ID/g) at 1 h, 7.9% ID/g at 4 h and 6.1% ID/g 6 h after injection. The radioactivity level in tumors was higher than in other organs and tissues except the kidneys (&#x0003e;30% ID/g). Blood levels were ~2% ID/g at 1 h, and 0.15% ID/g at 6 h. The biodistribution was characterized by quick clearance of radioactivity from blood and all organs and tissues. The radioactivity of intestine content was &#x0003c;3% ID/g at 6 h. Tumor/blood ratios were 6, 38, and 43 at 1, 4, and 6&#x000a0;h after injection, respectively. Pre-administration of Z<sub>HER2:342</sub> (83 nmol) decreased tumor accumulation from 7.9 &#x000b1; 1.0 to 0.30 &#x000b1; 0.07% ID/g (<i>P</i> &#x0003c;0.0001) at 4 h after injection. Biodistribution studies were also performed in normal NMRI mice (<i>n</i> = 4) without bearing any tumors at 4 h after injection. The results showed low accumulation in all organs and tissues except with 95% ID/g in the kidneys and ~3% ID in the intestines. Single-photon emission computed tomography (SPECT) analysis was performed in nude mice bearing the SKOV-3 tumors after i.v. injection of 3 MBq (81 &#x003bc;Ci) <sup>99m</sup>Tc-MaEEE. Tumor/muscle ratios were 8, 19, and 35 at 1, 2, and 5 h, respectively. No other organs were visualized except the kidneys. In mice pretreated with Z<sub>HER2:342</sub>, the tumors could not be clearly visualized with <sup>99m</sup>Tc-MaEEE-Z<sub>HER2:342</sub>. Tumor/muscle ratio was 3.6.as measured at 5 h after injection.</p></div><div id="Z-MaEEE-99mTc.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20and%20%28dog%20or%20pig%20or%20sheep%20or%20rabbit%29" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="Z-MaEEE-99mTc.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20and%20%28primate%20not%20human%29" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="Z-MaEEE-99mTc.Human_Studies"><h2 id="_Z-MaEEE-99mTc_Human_Studies_">Human Studies</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&#x00026;db=pubmed&#x00026;details_term=HER2%20342%20and%20human" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="Z-MaEEE-99mTc.References"><h2 id="_Z-MaEEE-99mTc_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.1">Carpenter G., Cohen S.
<em>Epidermal growth factor.</em>
<span><span class="ref-journal">J Biol Chem. </span>1990;<span class="ref-vol">265</span>(14):770912.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2186024" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 2186024</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.2">Yarden Y.
<em>The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities.</em>
<span><span class="ref-journal">Eur J Cancer. </span>2001;<span class="ref-vol">37</span> Suppl 4:S38.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11597398" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11597398</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.3">Rubin I., Yarden Y.
<em>The basic biology of HER2.</em>
<span><span class="ref-journal">Ann Oncol. </span>2001;<span class="ref-vol">12</span> Suppl 1:S38.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11521719" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11521719</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.4">Grunwald V., Hidalgo M.
<em>Developing inhibitors of the epidermal growth factor receptor for cancer treatment.</em>
<span><span class="ref-journal">J Natl Cancer Inst. </span>2003;<span class="ref-vol">95</span>(12):85167.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12813169" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12813169</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.5">Mendelsohn J.
<em>Anti-epidermal growth factor receptor monoclonal antibodies as potential anti-cancer agents.</em>
<span><span class="ref-journal">J Steroid Biochem Mol Biol. </span>1990;<span class="ref-vol">37</span>(6):88992.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2285602" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 2285602</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.6">Yasui W., Sumiyoshi H., Hata J., Kameda T., Ochiai A., Ito H., Tahara E.
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<span><span class="ref-journal">Cancer Res. </span>1988;<span class="ref-vol">48</span>(1):13741.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2446740" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 2446740</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.7">Ang K.K., Berkey B.A., Tu X., Zhang H.Z., Katz R., Hammond E.H., Fu K.K., Milas L.
<em>Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma.</em>
<span><span class="ref-journal">Cancer Res. </span>2002;<span class="ref-vol">62</span>(24):73506.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12499279" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12499279</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.8">Costa S., Stamm H., Almendral A., Ludwig H., Wyss R., Fabbro D., Ernst A., Takahashi A., Eppenberger U.
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<span><span class="ref-journal">Lancet. </span>1988;<span class="ref-vol">2</span>(8622):1258.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2903994" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 2903994</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.9">Ethier S.P.
<em>Growth factor synthesis and human breast cancer progression.</em>
<span><span class="ref-journal">J Natl Cancer Inst. </span>1995;<span class="ref-vol">87</span>(13):96473.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7629883" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 7629883</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.10">Yarden Y.
<em>Biology of HER2 and its importance in breast cancer.</em>
<span><span class="ref-journal">Oncology. </span>2001;<span class="ref-vol">61</span> Suppl 2:113.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11694782" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11694782</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.11">Carter P., Presta L., Gorman C.M., Ridgway J.B., Henner D., Wong W.L., Rowland A.M., Kotts C., Carver M.E., Shepard H.M.
<em>Humanization of an anti-p185HER2 antibody for human cancer therapy.</em>
<span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>1992;<span class="ref-vol">89</span>(10):42859.</span> [<a href="/pmc/articles/PMC49066/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC49066</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1350088" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 1350088</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.12">Perik P.J., Lub-De Hooge M.N., Gietema J.A., van der Graaf W.T., de Korte M.A., Jonkman S., Kosterink J.G., van Veldhuisen D.J., Sleijfer D.T., Jager P.L., de Vries E.G.
<em>Indium-111-labeled trastuzumab scintigraphy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.</em>
<span><span class="ref-journal">J Clin Oncol. </span>2006;<span class="ref-vol">24</span>(15):227682.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16710024" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 16710024</span></a>]</div></dd><dt>13.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.13">Lub-de Hooge M.N., Kosterink J.G., Perik P.J., Nijnuis H., Tran L., Bart J., Suurmeijer A.J., de Jong S., Jager P.L., de Vries E.G.
<em>Preclinical characterisation of 111In-DTPA-trastuzumab.</em>
<span><span class="ref-journal">Br J Pharmacol. </span>2004;<span class="ref-vol">143</span>(1):99106.</span> [<a href="/pmc/articles/PMC1575276/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC1575276</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15289297" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15289297</span></a>]</div></dd><dt>14.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.14">Garmestani K., Milenic D.E., Plascjak P.S., Brechbiel M.W.
<em>A new and convenient method for purification of 86Y using a Sr(II) selective resin and comparison of biodistribution of 86Y and 111In labeled Herceptin.</em>
<span><span class="ref-journal">Nucl Med Biol. </span>2002;<span class="ref-vol">29</span>(5):599606.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12088731" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 12088731</span></a>]</div></dd><dt>15.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.15">Smith-Jones P.M., Solit D., Afroze F., Rosen N., Larson S.M.
<em>Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET.</em>
<span><span class="ref-journal">J Nucl Med. </span>2006;<span class="ref-vol">47</span>(5):7936.</span> [<a href="/pmc/articles/PMC3193602/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC3193602</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16644749" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 16644749</span></a>]</div></dd><dt>16.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.16">Smith-Jones P.M., Solit D.B., Akhurst T., Afroze F., Rosen N., Larson S.M.
<em>Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors.</em>
<span><span class="ref-journal">Nat Biotechnol. </span>2004;<span class="ref-vol">22</span>(6):7016.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15133471" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15133471</span></a>]</div></dd><dt>17.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.17">Wikman M., Steffen A.C., Gunneriusson E., Tolmachev V., Adams G.P., Carlsson J., Stahl S.
<em>Selection and characterization of HER2/neu-binding affibody ligands.</em>
<span><span class="ref-journal">Protein Eng Des Sel. </span>2004;<span class="ref-vol">17</span>(5):45562.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15208403" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 15208403</span></a>]</div></dd><dt>18.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.18">Engfeldt, T., A. Orlova, T. Tran, A. Bruskin, C. Widstrom, A.E. Karlstrom, and V. Tolmachev, <em>Imaging of HER2-expressing tumours using a synthetic Affibody molecule containing the (99m)Tc-chelating mercaptoacetyl-glycyl-glycyl-glycyl (MAG3) sequence.</em> Eur J Nucl Med Mol Imaging, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17146656" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 17146656</span></a>]</div></dd><dt>19.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.19">Tran T., Engfeldt T., Orlova A., Widstrom C., Bruskin A., Tolmachev V., Karlstrom A.E.
<em>In vivo evaluation of cysteine-based chelators for attachment of 99mTc to tumor-targeting Affibody molecules.</em>
<span><span class="ref-journal">Bioconjug Chem. </span>2007;<span class="ref-vol">18</span>(2):54958.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17330952" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 17330952</span></a>]</div></dd><dt>20.</dt><dd><div class="bk_ref" id="Z-MaEEE-99mTc.REF.20">Tran T., Engfeldt T., Orlova A., Sandstrom M., Feldwisch J., Abrahmsen L., Wennborg A., Tolmachev V., Karlstrom A.E.
<em>(99m)Tc-maEEE-Z(HER2:342), an Affibody molecule-based tracer for the detection of HER2 expression in malignant tumors.</em>
<span><span class="ref-journal">Bioconjug Chem. </span>2007;<span class="ref-vol">18</span>(6):195664.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17944527" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 17944527</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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