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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="#__NBK22984_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK22984_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/GDCEP/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/GCIC/" 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="_NBK22984_"><span class="title" itemprop="name">Gd-DTPA <span class="small-caps">l</span>-Cystine bisamide copolymers</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">GCAC</div><p class="contrib-group"><span itemprop="author">Kenneth T. Cheng</span>, PhD, <span itemprop="author">Zheng-Rong Lu</span>, PhD, and <span itemprop="author">Todd Kaneshiro</span>, BS.</p><a data-jig="ncbitoggler" href="#__NBK22984_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK22984_ai__"><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><div class="contrib half_rhythm"><span itemprop="author">Zheng-Rong Lu</span>, PhD<div class="affiliation small">
|
||
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, Corresponding Author,
|
||
<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.hatu@ul.gnorgnehZ" class="oemail">ude.hatu@ul.gnorgnehZ</a>
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</div></div><div class="contrib half_rhythm"><span itemprop="author">Todd Kaneshiro</span>, BS<div class="affiliation small">
|
||
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT,
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||
<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude..hatu@orihsenaK.T" class="oemail">ude..hatu@orihsenaK.T</a>
|
||
</div></div></div><p class="small">Created: <span itemprop="datePublished">November 8, 2007</span>; Last Update: <span itemprop="dateModified">January 22, 2008</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="GCAC.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK22984/table/GCAC.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__GCAC.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;">Gd-DTPA <span class="small-caps">l</span>-Cystine bisamide copolymers</td><td rowspan="9" colspan="1" style="text-align:left;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK22984/bin/GCAC.jpg" alt="Image GCAC.jpg" /></div>
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</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;">GCAC</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;">Compound, polymers</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;">Non-targeted, vasculature, liver, kidneys.</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;">Nonspecific confinement to the vascular space</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;">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 contrast /signal:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Gadolinium (Gd)</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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<br />
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Gd-DTPA <span class="small-caps">l</span>-cystine bisamide copolymers structure.<br />Click on <a href="http://pubchem.ncbi.nlm.nih.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubChem</a> (<a href="http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46501388" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SID 46501388</a>) for more information.</td></tr></tbody></table></div></div><div id="GCAC.Background"><h2 id="_GCAC_Background_">Background</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers)+" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The Gd-DTPA <span class="small-caps">l</span>-cystine bisamide copolymer (GCAC) is a biodegradable, macromolecular contrast agent designed for contrast enhancement of the blood pool, liver, and kidneys for magnetic resonance imaging (MRI) (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>). The gadolinium(III) ion (Gd<sup>3+</sup>) is a paramagnetic lanthanide metal ion with seven unpaired electrons.</p><p>MRI signals depend on a wide range of parameters. The key factor of conventional MRI contrast is the interaction of the total water signal (proton density) and the magnetic properties of the tissues (<a class="bk_pop" href="#GCAC.EXTYLES.2">2</a>, <a class="bk_pop" href="#GCAC.EXTYLES.3">3</a>). Various paramagnetic and superparamagnetic contrast agents can increase the sensitivity and specificity of MRI. Current clinical agents are predominately Gd-based contrast agents (GBCA) and are largely nonspecific, low molecular weight compounds. These agents have transient tissue retention, a wide distribution into the extracellular space, and rapid excretion from the body (<a class="bk_pop" href="#GCAC.EXTYLES.3">3-5</a>). There is a need to develop intravascular MRI contrast agents that have a sufficiently long intravascular half-life (<i>t</i><sub>½</sub>) to allow imaging of the vasculature and aid in the detection of cancer and cardiovascular diseases (<a class="bk_pop" href="#GCAC.EXTYLES.6">6</a>, <a class="bk_pop" href="#GCAC.EXTYLES.7">7</a>).</p><p>Current strategies to prolong the intravascular <i>t</i><sub>½</sub> include the chelation of paramagnetic ions to macromolecules and the use of superparamagnetic nanoparticles (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>, <a class="bk_pop" href="#GCAC.EXTYLES.6">6</a>, <a class="bk_pop" href="#GCAC.EXTYLES.7">7</a>). Macromolecular contrast agents are generally large enough (>20 kDa) so that they do not readily diffuse across the healthy vascular endothelium and are not rapidly excreted. These agents are retained in the vasculature for a sufficiently prolonged period of time to allow for imaging, and they also preferentially accumulate in disease tissues with leaky vasculature, such as cancers and vascular disease. Most macromolecular GBCAs are prepared by the conjugation of Gd<sup>3+</sup> chelates to biomedical polymers including poly(amino) acids (<a class="bk_pop" href="#GCAC.EXTYLES.8">8</a>, <a class="bk_pop" href="#GCAC.EXTYLES.9">9</a>), polysaccharides (<a class="bk_pop" href="#GCAC.EXTYLES.10">10</a>, <a class="bk_pop" href="#GCAC.EXTYLES.11">11</a>), dendrimers (<a class="bk_pop" href="#GCAC.EXTYLES.12">12</a>, <a class="bk_pop" href="#GCAC.EXTYLES.13">13</a>), and proteins (<a class="bk_pop" href="#GCAC.EXTYLES.14">14</a>), or by the copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with diamines and the complexation with Gd<sup>3+</sup> (<a class="bk_pop" href="#GCAC.EXTYLES.15">15</a>, <a class="bk_pop" href="#GCAC.EXTYLES.16">16</a>). However, the development of these macromolecular GBCAs has been hampered by potential Gd toxicity associated with the slow degradation of chemically modified biomedical polymers (<a class="bk_pop" href="#GCAC.EXTYLES.6">6</a>, <a class="bk_pop" href="#GCAC.EXTYLES.17">17</a>). Smaller macromolecules (<20 kDa) are cleared more rapidly by the kidneys but their effectiveness may also be compromised. One approach to improve the safety of macromolecular GBCAs is the development of small molecules (<1.2 kDa) with a hydrophilic Gd<sup>3+</sup> complex and a hydrophobic region for reversible noncovalent binding to serum albumin (<a class="bk_pop" href="#GCAC.EXTYLES.6">6</a>, <a class="bk_pop" href="#GCAC.EXTYLES.18">18</a>). Lu et al. (<a class="bk_pop" href="#GCAC.EXTYLES.17">17</a>, <a class="bk_pop" href="#GCAC.EXTYLES.19">19</a>) proposed another approach by designing biodegradable macromolecular polydisulfide GBCAs. These agents have disulfide bonds incorporated into a polymeric backbone, and these bonds can be readily reduced by the thiol-disulfide exchange reaction with endogenous or exogenous thiols, such as glutathione and cysteine. As a result, these macromolecules are broken down into smaller complexes that are readily excreted by the kidneys. The Gd-DTPA-cystamine copolymer was the first such agent synthesized by the copolymerization of cystamine and DTPA dianhydride (<a class="bk_pop" href="#GCAC.EXTYLES.17">17</a>). A series of polydisulfide-based macromolecular GBCAs with different structural modifications around the disulfide bonds have been synthesized and evaluated by the same research team of Lu et al. (<a class="bk_pop" href="#GCAC.EXTYLES.17">17</a>, <a class="bk_pop" href="#GCAC.EXTYLES.20">20-23</a>). Kaneshiro et al. (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>) reported the synthesis and evaluation of GCAC and two other derivatives with different amide substituents at the cystine carboxylic groups. All three agents were cleaved <i>in vivo</i> into low molecular weight Gd<sup>3+</sup> chelates and were cleared rapidly in rats.</p><p>Both renal and extrarenal toxicities have been reported after the clinical use of GBCAs in patients with underlying kidney disease (<a class="bk_pop" href="#GCAC.EXTYLES.24">24-26</a>). In 2007, the <a href="http://www.fda.gov/cder/drug/infopage/gcca/default.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">US FDA</a> requested manufacturers of all GBCAs to add new warnings that exposure to GBCAs increases the risk for nephrogenic systemic fibrosis in patients with advanced kidney disease.</p></div><div id="GCAC.Synthesis"><h2 id="_GCAC_Synthesis_">Synthesis</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=((gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers)+)+AND+synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Kaneshiro et al. (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>) described the synthesis of GCAC from commercially available cystine bisamide. The DTPA <span class="small-caps">l</span>-cystine bisamide copolymer was first synthesized by condensation copolymerization of equimolar amounts of DTPA dianhydride and <span class="small-caps">l</span>-cystine bisamide. Briefly, cystine bisamide was dissolved in triethylamine (TEA) and anhydrous dimethyl sulfoxide (DMSO) while stirred in an ice-water bath at 5ºC. TEA acted as a base to neutralize the salts of monomers and as a solvent to increase the solubility of the copolymers. DTPA dianhydride was then added over a 25-min period. After 40 min, the solidified mixture was removed and allowed to come to room temperature. Additional DMSO was added and the mixture was stirred overnight at room temperature. DTPA <span class="small-caps">l</span>-cystine bisamide copolymers were precipitated in acetone and dissolved in double ionized water (DI H<sub>2</sub>O) at pH 7. The copolymer was dialyzed and concentrated to dryness. The resulting product was mixed with a large excess of Gd triacetate in DI H<sub>2</sub>O (pH 5.5) and stirred at room temperature for 1 h. Free Gd<sup>3+</sup> ions were removed by size-exclusion chromatography. The yield was 81%. The DTPA <span class="small-caps">l</span>-cystine bisamide copolymers were anionic and had a large hydrodynamic volume. The complexation of the copolymers with Gd<sup>3+</sup> ions produced a neutral GCAC with a significant reduction in hydrodynamic volume. Using size-exclusion chromatography, the number average molecular weight (<i>M</i><sub>n</sub>) and the weight average molecular weight (<i>M</i><sub>w</sub>) were determined to be 14.1 kDa and 22.3 kDa, respectively. The Gd content was determined to be 16.9% on the inductively coupled argon plasma optical emission spectrometer. This was lower than the calculated value of 20.4%; Kaneshiro et al. (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>) suggested that this difference might be attributed to the association of water molecules to the hydrophilic polymers.</p></div><div id="GCAC.In_Vitro_Studies_Tes"><h2 id="_GCAC_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=((gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers)+)+AND+(in+vitro)" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>The <i>in vitro</i> longitudinal relaxivity (R<sub>1</sub>) of GCAC based on T<sub>1</sub> relaxation time measurement at room temperature by a 3T scanner (inversion recovery prepared turbo spin-echo pulse sequence) was 4.37 mM−<sup>1</sup>s−<sup>1</sup> (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>). The <i>in vitro</i> transverse relaxivity (R<sub>2</sub>) was 6.21 mM−<sup>1</sup>s−<sup>1</sup>. In comparison, the R<sub>1</sub> of Gd-DTPA-BMEA was 4.62 mM−<sup>1</sup>s−<sup>1</sup>.</p><p>GCAC was stable in the solid state for at least 6 months of cold storage as its molecular weight distribution did not change.</p><p><i>In vitro</i> degradation of DTPA <span class="small-caps">l</span>-cystine bisamide copolymers (DCAC - copolymers without Gd) and GCAC with and without the presence of <span class="small-caps">l</span>-cysteine (15 μM) at 37ºC was studied (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>). In the presence of cysteine, DCAC completely degraded into low molecular weight species within 24 h. GCAC completely degraded into low molecular weight oligomers after 75 min. Measurement by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry indicated that the mass of degradation products with one or two repeat units was ~753.0 and ~1501.2 (<i>m/z</i>).</p></div><div id="GCAC.Animal_Studies"><h2 id="_GCAC_Animal_Studies_">Animal Studies</h2><div id="GCAC.Rodents"><h3>Rodents</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=((gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers)+)+AND+rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p><i>In vivo</i> metabolic studies of GCAC were conducted in rats with a dose of 0.1 mmol Gd/kg by i.v. injection (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>). Only one major metabolite with a mass (<i>m/z</i>) of 988.02 was identified in urine samples measured by positively-charged labeled MALDI-TOF mass spectrometry (α-cyano-4-hydroxycinnamic acid matrix) at 8 h. There were no major metabolites identified in urine samples at 24 h. With negatively-charged labeled MALDI-TOF mass spectrometry, the masses (<i>m/z</i>) identified in urine samples at 8 h were 589.06, 707.09, and 734.10. The structures of these metabolites were not known (<a class="bk_pop" href="#GCAC.EXTYLES.20">20</a>). No metabolites were observed at 24 h.</p><p><i>In vivo</i> MRI imaging was performed with a 3T MRI scanner in three rats (<a class="bk_pop" href="#GCAC.EXTYLES.1">1</a>). Each rat received an i.v. dose of 0.1 mmol Gd/kg. Images were obtained with a wrist coil using a 3D FLASH pulse sequence. Strong contrast enhancement was observed within the heart, blood vessels, liver, and kidneys at 2 min. The contrast enhancement gradually decreased but was still visible at 30 min. Contrast enhancement was also observed and gradually increased over time in the urinary bladder.</p></div><div id="GCAC.Other_NonPrimate_Mam"><h3>Other Non-Primate Mammals</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=((gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers)+)+AND+(dog+OR+rabbit+OR+pig+OR+sheep)" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="GCAC.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=((gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers)+)++AND+(primate+NOT+human)" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="GCAC.Human_Studies"><h2 id="_GCAC_Human_Studies_">Human Studies</h2><p>[<a href="/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=((gd+dtpa+l+cystine+bisamide+copolymer)+OR+(gd-dtpa-cystine+copolymers))+AND+human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="GCAC.NIH_Support"><h2 id="_GCAC_NIH_Support_">NIH Support</h2><p>R01 EB00489, R33 CA095873,</p></div><div id="GCAC.references"><h2 id="_GCAC_references_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.1">Kaneshiro T.L. , Ke T. , Jeong E.K. , Parker D.L. , Lu Z.R. Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging. <span><span class="ref-journal">Pharm Res. </span>2006;<span class="ref-vol">
|
||
<strong>23</strong>
|
||
</span>(6):1285–94.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16729223" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16729223</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.2">Morawski A.M. , Lanza G.A. , Wickline S.A. Targeted contrast agents for magnetic resonance imaging and ultrasound. <span><span class="ref-journal">Curr Opin Biotechnol. </span>2005;<span class="ref-vol">
|
||
<strong>16</strong>
|
||
</span>(1):89–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15722020" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15722020</span></a>]</div></dd><li><div class="bk_ref" id="GCAC.EXTYLES.3">3. Saini, S., J.T. Ferrucci, Enhanced Agents for Magnetic Resonance Imaging: Clinical Applications, in Pharmaceuticals in Medical Imaging, D.P. Swanson, H.M. Chilton and J.H. Thrall, Editor. 1990, MacMillan Publishing Co., Inc.: New York. p. 662-681.</div></li><li><div class="bk_ref" id="GCAC.EXTYLES.4">4. Brasch, R.C., M.D. Ogan and B.L. Engelstad, Paramagnetic Contrast Agents and Their Application in NMR Imaging, in Contrast media; Biologic effects and clinical application, Z. Parvez, R., R. Monada and M. Sovak, Editor. 1987, CRC Press, Inc.: Boca Raton, Florida. p. 131-143.</div></li><dt>5.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.5">Runge V.M. , Kirsch J.E. , Wells J.W. , Awh M.H. , Bittner D.F. , Woolfolk C.E. Enhanced liver MR: Contrast agents and imaging strategy. <span><span class="ref-journal">Critical Reviews in Diagnostic Imaging. </span>1993;<span class="ref-vol">
|
||
<strong>34</strong>
|
||
</span>(2):1–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8216813" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8216813</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.6">Mohs A.M. , Lu Z.R. Gadolinium(III)-based blood-pool contrast agents for magnetic resonance imaging: status and clinical potential. <span><span class="ref-journal">Expert Opin Drug Deliv. </span>2007;<span class="ref-vol">
|
||
<strong>4</strong>
|
||
</span>(2):149–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17335412" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17335412</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.7">Hyslop W.B. , Semelka R.C. Future directions in body magnetic resonance imaging. <span><span class="ref-journal">Top Magn Reson Imaging. </span>2005;<span class="ref-vol">
|
||
<strong>16</strong>
|
||
</span>(1):3–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16314694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16314694</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.8">Schuhmann-Giampieri G. , Schmitt-Willich H. , Frenzel T. , Press W.R. , Weinmann H.J. In vivo and in vitro evaluation of Gd-DTPA-polylysine as a macromolecular contrast agent for magnetic resonance imaging. <span><span class="ref-journal">Invest Radiol. </span>1991;<span class="ref-vol">
|
||
<strong>26</strong>
|
||
</span>(11):969–74.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1743920" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1743920</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.9">Weissleder R. , Bogdanov A. , Tung C.H. , Weinmann H.J. Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging. <span><span class="ref-journal">Bioconjug Chem. </span>2001;<span class="ref-vol">
|
||
<strong>12</strong>
|
||
</span>(2):213–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11312682" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11312682</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.10">Rongved P. , Klaveness J. Water-soluble polysaccharides as carriers of paramagnetic contrast agents for magnetic resonance imaging: synthesis and relaxation properties. <span><span class="ref-journal">Carbohydr Res. </span>1991;<span class="ref-vol">
|
||
<strong>214</strong>
|
||
</span>(2):315–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1769023" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1769023</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.11">Gibby W.A. , Bogdan A. , Ovitt T.W. Cross-linked DTPA polysaccharides for magnetic resonance imaging. Synthesis and relaxation properties. <span><span class="ref-journal">Invest Radiol. </span>1989;<span class="ref-vol">
|
||
<strong>24</strong>
|
||
</span>(4):302–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2745011" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2745011</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.12">Wiener E.C. , Brechbiel M.W. , Brothers H. , Magin R.L. , Gansow O.A. , Tomalia D.A. , Lauterbur P.C. Dendrimer-based metal chelates: a new class of magnetic resonance imaging contrast agents. <span><span class="ref-journal">Magn Reson Med. </span>1994;<span class="ref-vol">
|
||
<strong>31</strong>
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||
</span>(1):1–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8121264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8121264</span></a>]</div></dd><dt>13.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.13">Kobayashi H. , Sato N. , Kawamoto S. , Saga T. , Hiraga A. , Ishimori T. , Konishi J. , Togashi K. , Brechbiel M.W. 3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agent. <span><span class="ref-journal">Magn Reson Med. </span>2001;<span class="ref-vol">
|
||
<strong>46</strong>
|
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</span>(3):579–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11550252" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11550252</span></a>]</div></dd><dt>14.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.14">Lauffer R.B. , Brady T.J. Preparation and water relaxation properties of proteins labeled with paramagnetic metal chelates. <span><span class="ref-journal">Magn Reson Imaging. </span>1985;<span class="ref-vol">
|
||
<strong>3</strong>
|
||
</span>(1):11–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3923289" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3923289</span></a>]</div></dd><dt>15.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.15">Duarte M.G. , Gil M.H. , Peters J.A. , Colet J.M. , Elst L.V. , Muller R.N. , Geraldes C.F. Synthesis, characterization, and relaxivity of two linear Gd(DTPA)-polymer conjugates. <span><span class="ref-journal">Bioconjug Chem. </span>2001;<span class="ref-vol">
|
||
<strong>12</strong>
|
||
</span>(2):170–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11312677" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11312677</span></a>]</div></dd><dt>16.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.16">Ladd D.L. , Hollister R. , Peng X. , Wei D. , Wu G. , Delecki D. , Snow R.A. , Toner J.L. , Kellar K. , Eck J. , Desai V.C. , Raymond G. , Kinter L.B. , Desser T.S. , Rubin D.L. Polymeric gadolinium chelate magnetic resonance imaging contrast agents: design, synthesis, and properties. <span><span class="ref-journal">Bioconjug Chem. </span>1999;<span class="ref-vol">
|
||
<strong>10</strong>
|
||
</span>(3):361–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10346865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10346865</span></a>]</div></dd><dt>17.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.17">Lu Z.R. , Parker D.L. , Goodrich K.C. , Wang X. , Dalle J.G. , Buswell H.R. Extracellular biodegradable macromolecular gadolinium(III) complexes for MRI. <span><span class="ref-journal">Magn Reson Med. </span>2004;<span class="ref-vol">
|
||
<strong>51</strong>
|
||
</span>(1):27–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14705042" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14705042</span></a>]</div></dd><dt>18.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.18">Martin V.V. , Ralston W.H. , Hynes M.R. , Keana J.F. Gadolinium(III) di- and tetrachelates designed for in vivo noncovalent complexation with plasma proteins: a novel molecular design for blood pool MRI contrast enhancing agents. <span><span class="ref-journal">Bioconjug Chem. </span>1995;<span class="ref-vol">
|
||
<strong>6</strong>
|
||
</span>(5):616–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8974462" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8974462</span></a>]</div></dd><dt>19.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.19">Lu Z.R. , Mohs A.M. , Zong Y. , Feng Y. Polydisulfide Gd(III) chelates as biodegradable macromolecular magnetic resonance imaging contrast agents. <span><span class="ref-journal">Int J Nanomedicine. </span>2006;<span class="ref-vol">
|
||
<strong>1</strong>
|
||
</span>(1):31–40.</span> [<a href="/pmc/articles/PMC2426761/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2426761</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17722260" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17722260</span></a>]</div></dd><dt>20.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.20">Zong Y. , Wang X. , Goodrich K.C. , Mohs A.M. , Parker D.L. , Lu Z.R. Contrast-enhanced MRI with new biodegradable macromolecular Gd(III) complexes in tumor-bearing mice. <span><span class="ref-journal">Magn Reson Med. </span>2005;<span class="ref-vol">
|
||
<strong>53</strong>
|
||
</span>(4):835–42.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15799038" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15799038</span></a>]</div></dd><dt>21.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.21">Mohs A.M. , Wang X. , Goodrich K.C. , Zong Y. , Parker D.L. , Lu Z.R. PEG-g-poly(GdDTPA-co-L-cystine): a biodegradable macromolecular blood pool contrast agent for MR imaging. <span><span class="ref-journal">Bioconjug Chem. </span>2004;<span class="ref-vol">
|
||
<strong>15</strong>
|
||
</span>(6):1424–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15546211" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15546211</span></a>]</div></dd><dt>22.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.22">Wang X. , Feng Y. , Ke T. , Schabel M. , Lu Z.R. Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a biodegradable macromolecular magnetic resonance imaging contrast agent. <span><span class="ref-journal">Pharm Res. </span>2005;<span class="ref-vol">
|
||
<strong>22</strong>
|
||
</span>(4):596–602.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15846467" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15846467</span></a>]</div></dd><dt>23.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.23">Mohs A.M. , Zong Y. , Guo J. , Parker D.L. , Lu Z.R. PEG-g-poly(GdDTPA-co-L-cystine): effect of PEG chain length on in vivo contrast enhancement in MRI. <span><span class="ref-journal">Biomacromolecules. </span>2005;<span class="ref-vol">
|
||
<strong>6</strong>
|
||
</span>(4):2305–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16004476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16004476</span></a>]</div></dd><dt>24.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.24">Perazella M.A. , Rodby R.A. Gadolinium use in patients with kidney disease: a cause for concern. <span><span class="ref-journal">Semin Dial. </span>2007;<span class="ref-vol">
|
||
<strong>20</strong>
|
||
</span>(3):179–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17555477" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17555477</span></a>]</div></dd><dt>25.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.25">Grobner T. , Prischl F.C. <span><span class="ref-journal">and Gadolinium and nephrogenic systemic fibrosis. Kidney Int. </span>2007</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17507905" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17507905</span></a>]</div></dd><dt>26.</dt><dd><div class="bk_ref" id="GCAC.EXTYLES.26">Pedersen M. Safety update on the possible causal relationship between gadolinium-containing MRI agents and nephrogenic systemic fibrosis. <span><span class="ref-journal">J Magn Reson Imaging. </span>2007;<span class="ref-vol">
|
||
<strong>25</strong>
|
||
</span>(5):881–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17457808" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17457808</span></a>]</div></dd></dl></div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_top_margin"><div>This MICAD chapter is not included in the Open Access Subset, because it was authored / co-authored by one or more investigators who was not a member of the MICAD staff.</div></p></div></dd></dl></div><div id="bk_toc_contnr"></div></div></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/NBK22984/?report=reader">PubReader</a></li><li><a href="/books/NBK22984/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK22984" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK22984" style="display:none" title="Cite this Page"><div class="bk_tt">Cheng KT, Lu ZR, Kaneshiro T. Gd-DTPA l-Cystine bisamide copolymers. 2007 Nov 8 [Updated 2008 Jan 22]. 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/NBK22984/pdf/Bookshelf_NBK22984.pdf">PDF version of this page</a> (155K)</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="#GCAC.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#GCAC.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#GCAC.In_Vitro_Studies_Tes" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#GCAC.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#GCAC.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#GCAC.NIH_Support" ref="log$=inpage&link_id=inpage">NIH Support</a></li><li><a href="#GCAC.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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/><label for="__micad_btn_6">Any</label></div></form><form xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" name="frmGo" method="get" action="javascript:alert('frmGo:_@action_was_not_set')" id="frmGo"><input name="term" value="." type="hidden" /></form></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=1504834" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=1504834" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20641583" ref="ordinalpos=1&linkpos=1&log$=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> Gd-DTPA l-Cystine bisisopropyl amide copolymers.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span 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offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Gd-DTPA l-Cystine bispropyl amide copolymers.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Cheng KT, Lu ZR, Kaneshiro T. </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/16729223" ref="ordinalpos=1&linkpos=3&log$=relatedarticles&logdbfrom=pubmed">Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.</a><span class="source">[Pharm Res. 2006]</span><div class="brieflinkpop offscreen_noflow">Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Kaneshiro TL, Ke T, Jeong EK, Parker DL, Lu ZR. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Pharm Res. 2006 Jun; 23(6):1285-94. Epub 2006 Jun 1.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20641781" ref="ordinalpos=1&linkpos=4&log$=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> Gadobenate.</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> Gadobenate.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Cheng KT. </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/21735585" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Polyion complex micelles of poly(ethylene glycol)-b-poly(L-lysine)-gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-dextran sulfate.</a><span class="source">[Molecular Imaging and Contrast...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Polyion complex micelles of poly(ethylene glycol)-b-poly(L-lysine)-gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-dextran sulfate.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Shan L. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Molecular Imaging and Contrast Agent Database (MICAD). 2004</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=20641192" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=20641192" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d641ad2f30673f7b6445aa">Gd-DTPA l-Cystine bisamide copolymers - 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