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<title>64Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles - Molecular Imaging and Contrast Agent Database (MICAD) - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="Molecular Imaging and Contrast Agent Database (MICAD) [Internet]" /><meta name="citation_title" content="64Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2009/12/03" /><meta name="citation_author" content="Kam Leung" /><meta name="citation_pmid" content="20641755" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK23557/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="64Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="Kam Leung" /><meta name="DC.Date" content="2009/12/03" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK23557/" /><meta name="description" content="Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules. Water comprises ~80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal, and T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide (CLIO) nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, the paramagnetic T1 agents, such as gadolinium (Gd3+) and manganese (Mn2+), accelerate T1 relaxation and lead to brighter contrast images." /><meta name="og:title" content="64Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles" /><meta name="og:type" content="book" /><meta name="og:description" content="Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules. Water comprises ~80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal, and T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide (CLIO) nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. 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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="#__NBK23557_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK23557_dtls__"><div>Bethesda (MD): <a href="https://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>; 2004-2013.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/micad/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/micad/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/sosironoxidesvt68064cu/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/CuTNP/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK23557_"><span class="title" itemprop="name"><sup>64</sup>Cu-1,4,7,10-Tetraazacyclododecane-<i>N</i>,<i>N’</i>,<i>N’’</i>,<i>N’’’</i>-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm"><sup>64</sup>Cu-DOTA-IO-RGDyK</div><p class="contrib-group"><span itemprop="author">Kam Leung</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK23557_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK23557_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.mln.ibcn@dacim" class="oemail">vog.mln.ibcn@dacim</a></div></div></div></div><p class="small">Created: <span itemprop="datePublished">October 1, 2009</span>; Last Update: <span itemprop="dateModified">December 3, 2009</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="PASP_IO_cRGDyK64Cu.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK23557/table/PASP_IO_cRGDyK64Cu.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__PASP_IO_cRGDyK64Cu.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>64</sup>Cu-1,4,7,10-Tetraazacyclododecane-<i>N</i>,<i>N’</i>,<i>N’’</i>,<i>N’’’</i>-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles</td><td rowspan="9" colspan="1" style="text-align:center;vertical-align:middle;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Abbreviated name:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>64</sup>Cu-DOTA-IO-RGDyK</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Synonym:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Agent category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Peptide</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;">Integrin α<sub>v</sub>β<sub>3</sub></td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Target category:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Receptor-ligand 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;">Positron emission tomography (PET), magnetic resonance imaging (MRI)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Source of signal:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><sup>64</sup>Cu and iron oxide</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Activation:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No</td></tr><tr><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">
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<b>Studies:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul class="simple-list"><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" />
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<i>In vitro</i>
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</div></li><li class="half_rhythm"><div>
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<img alt="Checkbox" src="/corehtml/pmc/css/bookshelf/2.26/img/studies.checkbox.png" /> Rodents
|
||
</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&val=4504763" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">protein</a>, <a href="/entrez/viewer.fcgi?db=nucleotide&val=40217844" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nucleotide</a> (RefSeq), and <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=3685" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">gene</a> for more information about integrin α<sub>v</sub>β<sub>3</sub>.</td></tr></tbody></table></div></div><div id="PASP_IO_cRGDyK64Cu.Background"><h2 id="_PASP_IO_cRGDyK64Cu_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules. Water comprises ~80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (<i>T</i><sub>1</sub>, longitudinal, and <i>T</i><sub>2</sub>, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the <i>T</i><sub>1</sub> and <i>T</i><sub>2</sub> relaxation times of the surrounding nuclei, mainly the protons of water. <i>T</i><sub>2</sub>* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.1">1</a>). Cross-linked iron oxide (CLIO) nanoparticles and other iron oxide formulations affect <i>T</i><sub>2</sub> primarily and lead to decreased signals. On the other hand, the paramagnetic <i>T</i><sub>1</sub> agents, such as gadolinium (Gd<sup>3+</sup>) and manganese (Mn<sup>2+</sup>), accelerate <i>T</i><sub>1</sub> relaxation and lead to brighter contrast images.</p><p>Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.2">2</a>). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α<sub>v</sub>β<sub>3</sub> integrin is the most prominent receptor class affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.3" data-bk-pop-others="PASP_IO_cRGDyK64Cu.REF.4 PASP_IO_cRGDyK64Cu.REF.5 PASP_IO_cRGDyK64Cu.REF.6 PASP_IO_cRGDyK64Cu.REF.7 PASP_IO_cRGDyK64Cu.REF.8">3-8</a>). The α<sub>v</sub>β<sub>3</sub> integrin is strongly expressed on tumor cells and activated endothelial cells. In contrast, expression of α<sub>v</sub>β<sub>3</sub> integrin is weak on resting endothelial cells and most normal tissues. The α<sub>v</sub>β<sub>3</sub> antagonists are being studied as antitumor and antiangiogenic agents, and the agonists are being studied as angiogenic agents for coronary angiogenesis (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.7" data-bk-pop-others="PASP_IO_cRGDyK64Cu.REF.9 PASP_IO_cRGDyK64Cu.REF.10">7, 9, 10</a>). The tripeptide sequence Arg-Gly-Asp (RGD) is identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins including α<sub>v</sub>β<sub>3</sub>. Various radiolabeled cyclic RGD peptides have been introduced for imaging of tumors and tumor angiogenesis (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.11">11</a>). <sup>64</sup>Cu-1,4,7,10-Tetraazacyclododecane-<i>N</i>,<i>N’</i>,<i>N’’</i>,<i>N’’’</i>-tetraacetic acid-iron oxide-c(RGDyK) (<sup>64</sup>Cu-DOTA-IO-RGDyK) nanoparticles have been developed as a multimodality probe for positron emission tomography (PET) and MRI of tumor vasculature to study <i>in vivo</i> biodistribution of the tracer in tumor-bearing mice (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.12">12</a>). <sup>64</sup>Cu-DOTA-IO-RGDyK has been shown to have a high accumulation in the tumor vasculature with little extravastion and predominant liver and spleen accumulation.</p></div><div id="PASP_IO_cRGDyK64Cu.Synthesis"><h2 id="_PASP_IO_cRGDyK64Cu_Synthesis_">Synthesis</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD+synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Polyaspartic acid (PASP, 0.3 mmol) in ammonia was added to 0.6 M FeCl<sub>3</sub> and 0.3 M FeCl<sub>2</sub>. The mixture was heated for 1 h at 100°C (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.12">12</a>). PASP-Coated nanoparticles were purified with dialysis. DOTA was activated with ethyl-3-dimethylaminopropyl-carbodiimide and sulfo-<i>N</i>-hydroxysuccinimide for 30 min. The activated DOTA (800 nmol) and the bifunctional linker NHS-poly(ethylene glycol-maleimide (1,200 nmol) were added to a solution of PASP-coated nanoparticles (0.039 mmol iron concentration). The mixture was incubated for 60 min at 4°C. c(RGDyK)-SH (1,500 nmol) was incubated with the mixture overnight at room temperature. DOTA-IO-RGDyK nanoparticles were purified with column chromatography and dialysis. DOTA-IO-RGDyK nanoparticles and <sup>64</sup>CuCl<sub>2</sub> in acetate buffer (pH 6.5) were incubated for 40 min at 40°C. <sup>64</sup>Cu-DOTA-IO-RGDyK nanoparticles were isolated with column chromatography. The average size of DOTA-IO-RGDyK nanoparticles was 45 ± 10 nm in buffer as measured with transmission electron microscope. Each particle contained ~35 c(RGDyK) molecules and ~30 DOTA-chelating groups. <sup>64</sup>Cu-DOTA-IO-RGDyK nanoparticles had a specific activity of 185 GBq/g of iron (5 Ci/g of iron).</p></div><div id="PASP_IO_cRGDyK64Cu.In_Vitro_Studies_Tes"><h2 id="_PASP_IO_cRGDyK64Cu_In_Vitro_Studies_Tes_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD+in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Lee et al. (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.12">12</a>) performed a competitive cell-binding assay using human glioblastoma U87MG tumor cells (expressing α<sub>v</sub>β<sub>3</sub>). DOTA-IO-RGDyK nanoparticles inhibited the binding of <sup>125</sup>I-echistatin in a dose-dependent manner with a 50% inhibition concentration of 34 ± 5 nM, which was ~6-fold lower than that of c(RGDyK). DOTA-IO nanoparticles had no inhibitory effect on the binding assay. IO nanoparticles exhibited a <i>T</i><sub>2</sub> relaxivity <i>r</i><sub>2</sub> value (at 3 T) of 105.5 mM<sup>-1</sup>s<sup>-1</sup>, whereas ferumoxide exhibited a <i>r</i><sub>2</sub> value of 151.9 mM<sup>-1</sup> s<sup>-1</sup>.</p></div><div id="PASP_IO_cRGDyK64Cu.Animal_Studies"><h2 id="_PASP_IO_cRGDyK64Cu_Animal_Studies_">Animal Studies</h2><div id="PASP_IO_cRGDyK64Cu.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD+rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Lee et al. (<a class="bk_pop" href="#PASP_IO_cRGDyK64Cu.REF.12">12</a>) used a whole-body PET imaging system to study the accumulation of 3.7 MBq (0.1 mCi) <sup>64</sup>Cu-DOTA-IO-c(RGDyK) or <sup>64</sup>Cu-DOTA-IO in nude mice bearing U87MG tumors. <sup>64</sup>Cu-DOTA-IO-c(RGDyK) (300 µg of iron) was injected intravenously into tumor-bearing mice (<i>n</i> = 3/group). Tumor accumulation of <sup>64</sup>Cu-DOTA-IO-c(RGDyK) was 7.9% injected dose/gram (ID/g) at 1 h, 10.1% ID/g at 4 h, and 9.8% ID/g at 21 h. <sup>64</sup>Cu-DOTA-IO showed tumor accumulation of <5% ID/g at these time points. There was no difference in accumulation at 4 h in the liver (23% ID/g) and kidney (5% ID/g) between the two nanoparticles. Co-injection of c(RGDyK) (10 mg/kg) with <sup>64</sup>Cu-DOTA-IO-c(RGDyK) reduced the tumor radioactivity levels to <4% ID/g at these time points. <i>T</i><sub>2</sub>-Weighted MRI studies at 3 T were performed in mice bearing U87MG tumors after intravenous injection of DOTA-IO-c(RGDyK) nanoparticles. There was a greater tumor signal reduction in the mice receiving DOTA-IO-c(RGDyK) nanoparticles as compared with that in mice receiving DOTA-IO nanoparticles or co-injection of DOTA-IO-RGDyK at 4 h after injection. The strong contrast reduction was similar in the liver and spleen for both nanoparticles. Staining of iron in tissue sections confirmed the MRI findings.</p></div><div id="PASP_IO_cRGDyK64Cu.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD+and%20%28dog%20or%20pig%20or%20sheep%20or%20rabbit%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="PASP_IO_cRGDyK64Cu.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD+and%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="PASP_IO_cRGDyK64Cu.Human_Studies"><h2 id="_PASP_IO_cRGDyK64Cu_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=Iron+oxide+RGD+human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="PASP_IO_cRGDyK64Cu.NIH_Support"><h2 id="_PASP_IO_cRGDyK64Cu_NIH_Support_">NIH Support</h2><p>R24 CA93862, P50 CA114747, R01 CA119053, R21 CA102123, R21 CA121842, U54 CA119367</p></div><div id="PASP_IO_cRGDyK64Cu.References"><h2 id="_PASP_IO_cRGDyK64Cu_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.1">Wang Y.X., Hussain S.M., Krestin G.P.
|
||
<em>Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging.</em>
|
||
<span><span class="ref-journal">Eur Radiol. </span>2001;<span class="ref-vol">11</span>(11):2319–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11702180" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11702180</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.2">Hynes R.O.
|
||
<em>Integrins: versatility, modulation, and signaling in cell adhesion.</em>
|
||
<span><span class="ref-journal">Cell. </span>1992;<span class="ref-vol">69</span>(1):11–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1555235" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1555235</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.3">Jin H., Varner J.
|
||
<em>Integrins: roles in cancer development and as treatment targets.</em>
|
||
<span><span class="ref-journal">Br J Cancer. </span>2004;<span class="ref-vol">90</span>(3):561–5.</span> [<a href="/pmc/articles/PMC2410157/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2410157</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14760364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14760364</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.4">Varner J.A., Cheresh D.A.
|
||
<em>Tumor angiogenesis and the role of vascular cell integrin alphavbeta3.</em>
|
||
<span><span class="ref-journal">Important Adv Oncol. </span>1996:69–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8791129" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8791129</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.5">Wilder R.L.
|
||
<em>Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases.</em>
|
||
<span><span class="ref-journal">Ann Rheum Dis. </span>2002;<span class="ref-vol">61</span> Suppl 2:ii96–9.</span> [<a href="/pmc/articles/PMC1766704/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1766704</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12379637" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12379637</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.6">Grzesik W.J.
|
||
<em>Integrins and bone--cell adhesion and beyond.</em>
|
||
<span><span class="ref-journal">Arch Immunol Ther Exp (Warsz). </span>1997;<span class="ref-vol">45</span>(4):271–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9523000" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9523000</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.7">Kumar C.C.
|
||
<em>Integrin alpha v beta 3 as a therapeutic target for blocking tumor-induced angiogenesis.</em>
|
||
<span><span class="ref-journal">Curr Drug Targets. </span>2003;<span class="ref-vol">4</span>(2):123–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12558065" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12558065</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.8">Ruegg C., Dormond O., Foletti A.
|
||
<em>Suppression of tumor angiogenesis through the inhibition of integrin function and signaling in endothelial cells: which side to target?</em>
|
||
<span><span class="ref-journal">Endothelium. </span>2002;<span class="ref-vol">9</span>(3):151–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12380640" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12380640</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.9">Kerr J.S., Mousa S.A., Slee A.M.
|
||
<em>Alpha(v)beta(3) integrin in angiogenesis and restenosis.</em>
|
||
<span><span class="ref-journal">Drug News Perspect. </span>2001;<span class="ref-vol">14</span>(3):143–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12819820" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12819820</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.10">Mousa S.A.
|
||
<em>alphav Vitronectin receptors in vascular-mediated disorders.</em>
|
||
<span><span class="ref-journal">Med Res Rev. </span>2003;<span class="ref-vol">23</span>(2):190–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12500288" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12500288</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.11">Haubner R., Wester H.J.
|
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<em>Radiolabeled tracers for imaging of tumor angiogenesis and evaluation of anti-angiogenic therapies.</em>
|
||
<span><span class="ref-journal">Curr Pharm Des. </span>2004;<span class="ref-vol">10</span>(13):1439–55.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15134568" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15134568</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="PASP_IO_cRGDyK64Cu.REF.12">Lee H.Y., Li Z., Chen K., Hsu A.R., Xu C., Xie J., Sun S., Chen X.
|
||
<em>PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles.</em>
|
||
<span><span class="ref-journal">J Nucl Med. </span>2008;<span class="ref-vol">49</span>(8):1371–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18632815" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18632815</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK23557</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/20641755" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">20641755</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/micad/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/micad/sosironoxidesvt68064cu/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/CuTNP/" title="Next page in this title">Next ></a></div></div></div></div>
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<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK23557&db=books">Share</a></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK23557/?report=reader">PubReader</a></li><li><a href="/books/NBK23557/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK23557" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK23557" style="display:none" title="Cite this Page"><div class="bk_tt">Leung K. 64Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-iron oxide-c(RGDyK) nanoparticles. 2009 Oct 1 [Updated 2009 Dec 3]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK23557/pdf/Bookshelf_NBK23557.pdf">PDF version of this page</a> (139K)</li><li><a href="/books/n/micad/toc/bin/micad.csv">MICAD summary (CSV file)</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#PASP_IO_cRGDyK64Cu.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#PASP_IO_cRGDyK64Cu.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#PASP_IO_cRGDyK64Cu.In_Vitro_Studies_Tes" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#PASP_IO_cRGDyK64Cu.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#PASP_IO_cRGDyK64Cu.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#PASP_IO_cRGDyK64Cu.NIH_Support" ref="log$=inpage&link_id=inpage">NIH Support</a></li><li><a href="#PASP_IO_cRGDyK64Cu.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Search MICAD</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-application" id="Shutter"></a></div><div class="portlet_content"><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmSearch" method="get" action="/books/NBK5330/" id="frmSearch"><script type="text/javascript" src="/corehtml/pmc//js/bookshelf/micad.js">/**/</script><label class="offscreen_noflow" for="txtfield">Search term</label><input id="txtfield" type="text" name="f1_term" size="22" onKeyPress="KeyPress('micad',event,'/books/NBK5330/','')" /><button name="f1_search" type="submit">Go</button><button onclick="this.form.reset();" type="reset">Clear</button><p><b>Limit my Search:</b></p><div class="clearfix"><label for="detection">Method of detection:</label><div class="right"><select name="detection" id="detection" style="width:200px"><option value="" selected="selected">Any</option><option value="(MRI OR "Magnetic resonance imaging" OR MRS)">MRI</option><option value="Multimodal">Multimodal imaging</option><option value="Optical">Optical imaging</option><option value="PET">PET</option><option value="Photoacoustic">Photoacoustic imaging</option><option value="(SPECT OR planar)">SPECT</option><option value="Ultrasound">Ultrasound</option><option value="(x-ray OR ct)">X-ray, CT</option></select></div></div><div class="clearfix"><label for="signal">Source of signal/contrast:</label><div class="right"><select name="signal" id="signal" style="width:200px"><option value="" selected="selected">Any</option><optgroup label="MRI agents"><option value="(Copper OR Cu)">Copper</option><option value="(Europium OR Eu3+)">Europium</option><option value="(Fluorine OR 19F)">Fluorine</option><option value="(Gadolinium OR Gd3+)">Gadolinium</option><option value=""Hyperpolarized 13C"">Hyperpolarized 13C</option><option value=""Iron oxide"">Iron oxide</option><option value=""Nitroxide radicals"">Nitroxide radicals</option><option value="(Oxygen OR 17O)">Oxygen</option><option value="Thulium">Thulium</option></optgroup><optgroup label="Multimodal agents"><option value="((Gadolinium OR Gd3+) AND Optical)">Gadolinium and optical</option><option value="((Gadolinium OR Gd3+) AND (Gold OR Au))">Gadolinium and Gold</option><option value="("Iron oxide" AND (64Cu OR 124I OR 111In))">Iron oxide and
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href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=1947868" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/23720861" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-icosahedral closo-borane(12) scaffold conjugated with Glu-{Glu-[cyclo(Arg-Gly-Asp-d-Phe-Lys)](2)}(2).</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-icosahedral closo-borane(12) scaffold conjugated with Glu-{Glu-[cyclo(Arg-Gly-Asp-d-Phe-Lys)](2)}(2).<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Leung K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20641544" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cyclo(Arg-Gly-Asp-D-Try-Glu) conjugated to ultrasmall superparamagnetic iron oxide nanoparticles.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cyclo(Arg-Gly-Asp-D-Try-Glu) conjugated to ultrasmall superparamagnetic iron oxide nanoparticles.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Leung K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20641486" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Gadolinium diethylenetriamine pentaacetic acid-Arg-Gly-Asp peptidomimetic.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Gadolinium diethylenetriamine pentaacetic acid-Arg-Gly-Asp peptidomimetic.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Leung K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20641887" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (64)Cu-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-quantum dot-c(Arg-Gly-Asp-D-Tyr-Lys).</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (64)Cu-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-quantum dot-c(Arg-Gly-Asp-D-Tyr-Lys).<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Leung K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21249762" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (64)Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-Lys(Cy5.5)-Gly-Gly-Tyr-knottin 2.5D.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> (64)Cu-1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-Lys(Cy5.5)-Gly-Gly-Tyr-knottin 2.5D.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Leung K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=20641755" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=20641755" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div 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