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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="Folate-polyethylene glycol-ultrasmall superparamagnetic iron oxide nanoparticles" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2011/07/14" /><meta name="citation_author" content="Kam Leung" /><meta name="citation_pmid" content="21755636" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK56365/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Folate-polyethylene glycol-ultrasmall superparamagnetic iron oxide 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="2011/07/14" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK56365/" /><meta name="description" content="Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. 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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 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="#__NBK56365_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK56365_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/EBDTPAGd/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/Gadobenate/" 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="_NBK56365_"><span class="title" itemprop="name">Folate-polyethylene glycol-ultrasmall superparamagnetic iron oxide nanoparticles</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">P1133</div><p class="contrib-group"><span itemprop="author">Kam Leung</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK56365_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK56365_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">May 9, 2011</span>; Last Update: <span itemprop="dateModified">July 14, 2011</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="P1133.T.nc_chemical_namefolatepolyethyle" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56365/table/P1133.T.nc_chemical_namefolatepolyethyle/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__P1133.T.nc_chemical_namefolatepolyethyle_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;">Folate-polyethylene glycol-ultrasmall superparamagnetic iron oxide 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;">P1133</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</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;">Folate receptor</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</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 signal:</b>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">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
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</div></li></ul>
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</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Structure is not available in <a href="http://pubchem.ncbi.nlm.nih.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubChem</a>.</td></tr></tbody></table></div></div><div id="P1133.Background"><h2 id="_P1133_Background_">Background</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133" 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, which comprise ~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 development 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 (<a class="bk_pop" href="#P1133.REF.1">1</a>). Cross-linked iron oxide nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd<sup>3+</sup>) and manganese (Mn<sup>2+</sup>), accelerate T1 relaxation and lead to brighter contrast images.</p><p>The superparamagnetic iron oxide (SPIO) structure is composed of ferric iron (Fe<sup>3+</sup>) and ferrous iron (Fe<sup>2+</sup>). The iron oxide particles are coated with a protective layer of dextran or another polysaccharide. These particles have large combined magnetic moments or spins, which are randomly rotated in the absence of an applied magnetic field. SPIO is used mainly as a T2 contrast agent in MRI, though it can shorten both T1 and T2/T2* relaxation processes. SPIO particle uptake into the reticuloendothelial system (RES) is by endocytosis or phagocytosis. SPIO particles are also taken up by phagocytic cells such as monocytes, macrophages, and oligodendroglial cells. A variety of cells can also be labeled with these particles for cell trafficking and tumor-specific imaging studies. SPIO agents are classified by their sizes with coating material, which can range from ~10 to 3,500 nm in diameter, as large SPIO nanoparticles, standard SPIO nanoparticles, ultrasmall SPIO (USPIO) nanoparticles, and monocrystalline iron oxide nanoparticles (1). </p><p>Folic acid is a water-soluble B vitamin (<a class="bk_pop" href="#P1133.REF.2">2</a>) that is essential for methylation and DNA synthesis. The primary pathway for folate entry into cells is through the facilitated transporter, which has a low affinity for folate (Michaelis constant (<i>K</i><sub>m</sub>) = 1–5 μM). Some cells in the choroid plexus, kidney, lung, thyroid, spleen, placenta, and thymus also possess a higher-affinity receptor (dissociation constant (<i>K</i><sub>d</sub>) = 0.5 nM) that allows folate uptake <i>via</i> receptor-mediated endocytosis. Some human epithelial tumor cells have been found to overexpress folate-binding protein (<a class="bk_pop" href="#P1133.REF.3">3</a>). More than 90% of human ovarian and endometrial cancers express the high-affinity receptor, which is absent in the respective normal tissues. Breast, colorectal, renal, and lung carcinomas also overexpress the folate receptor but at lower frequencies (20%–50%). Activated macrophages, but not resting macrophages, have also been found to express the folate receptor (<a class="bk_pop" href="#P1133.REF.4">4</a>). Several folate-based conjugates have been studied in tumor imaging [<a href="/pubmed?term=%28%22folic%20acid%22%5BMeSH%20Terms%5D%20OR%20%28%22folic%22%5BAll%20Fields%5D%20AND%20%22acid%22%5BAll%20Fields%5D%29%20OR%20%22folic%20acid%22%5BAll%20Fields%5D%20OR%20%22folate%22%5BAll%20Fields%5D%29%20AND%20%28%22Receptor%22%5BJournal%5D%20OR%20%22receptor%22%5BAll%20Fields%5D%29%20AND%20%28%22molecular%20imaging%22%5BMeSH%20Terms%5D%20OR%20%28%22molecular%22%5BAll%20Fields%5D%20AND%20%22imaging%22%5BAll%20Fields%5D%29%20OR%20%22molecular%20imaging%22%5BAll%20Fiel" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>].</p><p>USPIO iron nanoparticles have diameters of 4–6 nm, and the hydrodynamic diameters with dextran or polyethylene glycol (PEG) coating are 20–50 nm. USPIO nanoparticles have a long plasma half-life because of their small size. The blood pool half-life is calculated to be ~24 h in humans (<a class="bk_pop" href="#P1133.REF.5">5</a>) and 2 h in mice (<a class="bk_pop" href="#P1133.REF.6">6</a>). Because of its long blood half-life, USPIO can be used as a blood pool agent during the early phase of intravenous administration (<a class="bk_pop" href="#P1133.REF.7">7</a>). In the late phase, USPIO is suitable for the evaluation of the RES in the body, particularly in the lymph nodes (<a class="bk_pop" href="#P1133.REF.8">8</a>). Various ligands and antibody-conjugated USPIO nanoparticles have been studied for <i>in vivo</i> targeted MRI in small animals (<a class="bk_pop" href="#P1133.REF.9" data-bk-pop-others="P1133.REF.10">9, 10</a>). Meier et al. (<a class="bk_pop" href="#P1133.REF.11">11</a>) performed <i>in vivo</i> MRI of breast cancer in mice using folate-conjugated PEG-USPIO nanoparticles (P1133).</p><div id="P1133.Related_Resource_Links"><h3>Related Resource Links:</h3><ul><li class="half_rhythm"><div>Chapters in MICAD (<a href="/sites/entrez?db=Books&cmd=Search&term=folate+AND+micad%5bbook%5d&doptcmdl=TOCView&log%24=booksrch&bname=micad" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Folate</a>)</div></li><li class="half_rhythm"><div>Gene information in NCBI (<a href="/gene/2348" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Folate receptor</a>)</div></li><li class="half_rhythm"><div>Articles in Online Mendelian Inheritance in Man (OMIM) (<a href="/omim/136430" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Folate receptor</a>)</div></li><li class="half_rhythm"><div>Clinical trials (<a href="http://www.clinicaltrials.gov/ct2/results?term=folate+receptor" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Folate receptor</a>, <a href="http://www.clinicaltrials.gov/ct2/results?term=uspio" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">USPIO</a>)</div></li><li class="half_rhythm"><div>Drug information in FDA (<a href="http://google2.fda.gov/search?q=folate+receptor&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&output=xml_no_dtd&getfields=*&x=14&y=15" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Folate receptor</a>)</div></li></ul></div></div><div id="P1133.Synthesis"><h2 id="_P1133_Synthesis_">Synthesis</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133%20and%20synthesis" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Meier et al. (<a class="bk_pop" href="#P1133.REF.11">11</a>) prepared folate-PEG-amine by reaction of folic acid with PEG-bis-amine in anhydrous dimethyl sulfoxide with diisopropylcarbodiimide/<i>N</i>-hydroxysuccinimide. Folate-PEG-amine was purified with column chromatography. Folate-PEG-amine was added to carboxylate-USPIO nanoparticles. The product, P1133, had a mean hydrodynamic diameter of 26 nm. There were 8–10 folate moieties per nanoparticle. P904 (PEG-USPIO without folate; diameter, 21 nm) was also prepared as a control. P1133 exhibited an r1 relaxivity value of 12 mM<sup>-1</sup>s<sup>-1</sup> and an r2 relaxivity value of 95 mM<sup>-1</sup>s<sup>-1</sup> in water at 60 MHz. P904 showed r1 and r2 relaxivity values similar to those of P1133.</p></div><div id="P1133.In_Vitro_Studies_Testing_in_Cells"><h2 id="_P1133_In_Vitro_Studies_Testing_in_Cells_"><i>In Vitro</i> Studies: Testing in Cells and Tissues</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133%20and%20in%20vitro" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Cells from human breast cancer cell line MDA-MB-231 express high levels of mRNA for folate receptor, whereas cells from the human lung carcinoma A549 have no detectable level (<a class="bk_pop" href="#P1133.REF.11">11</a>). MDA-MB-231 cells (10 × 10<sup>6</sup>) were incubated with 50 µM P1133 and P904 with or without 750 µM folate for 24 h. P1133-Labeled MDA-MB-231 cells showed an iron uptake of 8.2 pg/cell, which was inhibited to 4.7 pg/cell with excess folate (<i>P</i> = 0.002). P904-Labeled cells (with or without excess folate) showed an iron uptake of 1.5 pg/cell. Untreated control cells showed iron levels of 0.68–0.73 pg/cell. The cell viability of P1133-labeled cells (95 ± 3%) was not significantly different from that of P904-labeled cells (97 ± 2%). MRI showed that P1133-labeled cells exhibited R2 relaxation rates of 0.0172 ms<sup>-1</sup> and 0.0116 ms<sup>-1</sup> without and with excess folate, respectively. Excess folate blocked uptake of P1133. P904-Labeled cells (with or without excess folate) showed R2 relaxation rates of ~0.0075–0.0079 ms<sup>-1</sup>, indicating that folate had little effect on the control P904. Untreated control cells showed R2 relaxation rates of 0.0071–0.0075 ms<sup>-1</sup>.</p></div><div id="P1133.Animal_Studies"><h2 id="_P1133_Animal_Studies_">Animal Studies</h2><div id="P1133.Rodents"><h3>Rodents</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133%20and%20rodentia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>Meier et al. (<a class="bk_pop" href="#P1133.REF.11">11</a>) performed a series of whole-body 3-T MRI (T2-weighted) in nude mice (<i>n</i> = 6) bearing MDA-MB-231 or A549 tumors after intravenous injection of 0.5 mmol Fe/kg P1133 and P904. Folate receptor–positive MDA-MB-231 tumors showed a moderate decline (<i>P</i> < 0.05) in signal/noise ratio (SNR) during the early phase (1 h) after injection of P1133 (21.1 ± 6.2) and P904 (19.7 ± 3.2) as compared with pre-injection (P1133 = 28.9 ± 6.0 and P904 = 27.4 ± 3.9). At 24 h, there was a persistent negative enhancement with P1133 (SNR = 14.9 ± 2.5, <i>P</i> = 0.011) but not with P904 (SNR = 27.0 ± 3.8, <i>P</i> = 0.29). The early-phase (1 h) negative enhancement was due to non-target perfusion retention in the tumors, and the later-phase (24 h) enhancement was due to P1133 targeting the folate receptor–positive tumors. On the other hand, folate receptor–negative A549 tumors showed a minor negative enhancement during the early phase and did not show a persistent negative enhancement during the later phase. Immunohistochemical staining confirmed the presence of folate receptors in MDA-MB-231 tumors and the absence of folate receptors in A549 tumors. P1133-Treated MDA-MB-231 tumors exhibited intracellular and extracellular retention of iron particles, but the same was not observed in P1133-treated A549 tumors, P904-treated MDA-MD-231 tumors, or P904-treated A549 tumors.</p></div><div id="P1133.Other_NonPrimate_Mammals"><h3>Other Non-Primate Mammals</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133%20and%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="P1133.NonHuman_Primates"><h3>Non-Human Primates</h3><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133%20and%20%28primate%20not%20human%29" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div></div><div id="P1133.Human_Studies"><h2 id="_P1133_Human_Studies_">Human Studies</h2><p>[<a href="/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=P1133%20and%20human" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</p><p>No publication is currently available.</p></div><div id="P1133.References"><h2 id="_P1133_References_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="P1133.REF.1">Wang Y.X., Hussain S.M., Krestin G.P.
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<em>Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging.</em>
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<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="P1133.REF.2">Stanger O.
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<em>Physiology of folic acid in health and disease.</em>
|
||
<span><span class="ref-journal">Curr Drug Metab. </span>2002;<span class="ref-vol">3</span>(2):211–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12003352" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12003352</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="P1133.REF.3">Ke C.Y., Mathias C.J., Green M.A.
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<em>The folate receptor as a molecular target for tumor-selective radionuclide delivery.</em>
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||
<span><span class="ref-journal">Nucl Med Biol. </span>2003;<span class="ref-vol">30</span>(8):811–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14698784" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14698784</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="P1133.REF.4">Nakashima-Matsushita N., Homma T., Yu S., Matsuda T., Sunahara N., Nakamura T., Tsukano M., Ratnam M., Matsuyama T.
|
||
<em>Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis.</em>
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||
<span><span class="ref-journal">Arthritis Rheum. </span>1999;<span class="ref-vol">42</span>(8):1609–16.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10446858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10446858</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="P1133.REF.5">McLachlan S.J., Morris M.R., Lucas M.A., Fisco R.A., Eakins M.N., Fowler D.R., Scheetz R.B., Olukotun A.Y.
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<em>Phase I clinical evaluation of a new iron oxide MR contrast agent.</em>
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||
<span><span class="ref-journal">J Magn Reson Imaging. </span>1994;<span class="ref-vol">4</span>(3):301–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8061425" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8061425</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="P1133.REF.6">Weissleder R., Elizondo G., Wittenberg J., Rabito C.A., Bengele H.H., Josephson L.
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<em>Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging.</em>
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<span><span class="ref-journal">Radiology. </span>1990;<span class="ref-vol">175</span>(2):489–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2326474" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2326474</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="P1133.REF.7">Stillman A.E., Wilke N., Li D., Haacke M., McLachlan S.
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<em>Ultrasmall superparamagnetic iron oxide to enhance MRA of the renal and coronary arteries: studies in human patients.</em>
|
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<span><span class="ref-journal">J Comput Assist Tomogr. </span>1996;<span class="ref-vol">20</span>(1):51–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8576482" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8576482</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="P1133.REF.8">Anzai Y., Piccoli C.W., Outwater E.K., Stanford W., Bluemke D.A., Nurenberg P., Saini S., Maravilla K.R., Feldman D.E., Schmiedl U.P., Brunberg J.A., Francis I.R., Harms S.E., Som P.M., Tempany C.M.
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||
<em>Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study.</em>
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<span><span class="ref-journal">Radiology. </span>2003;<span class="ref-vol">228</span>(3):777–88.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12954896" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12954896</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="P1133.REF.9">Boutry S., Laurent S., Elst L.V., Muller R.N.
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<em>Specific E-selectin targeting with a superparamagnetic MRI contrast agent.</em>
|
||
<span><span class="ref-journal">Contrast Media Mol Imaging. </span>2006;<span class="ref-vol">1</span>(1):15–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17193596" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17193596</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="P1133.REF.10">Schellenberger E.A., Sosnovik D., Weissleder R., Josephson L.
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<em>Magneto/optical annexin V, a multimodal protein.</em>
|
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<span><span class="ref-journal">Bioconjug Chem. </span>2004;<span class="ref-vol">15</span>(5):1062–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15366960" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15366960</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="P1133.REF.11">Meier R., Henning T.D., Boddington S., Tavri S., Arora S., Piontek G., Rudelius M., Corot C., Daldrup-Link H.E.
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<em>Breast cancers: MR imaging of folate-receptor expression with the folate-specific nanoparticle P1133.</em>
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<span><span class="ref-journal">Radiology. </span>2010;<span class="ref-vol">255</span>(2):527–35.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20413763" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20413763</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: NBK56365</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/21755636" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">21755636</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/EBDTPAGd/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/micad/Gadobenate/" title="Next page in this title">Next ></a></div></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/NBK56365/?report=reader">PubReader</a></li><li><a href="/books/NBK56365/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK56365" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK56365" style="display:none" title="Cite this Page"><div class="bk_tt">Leung K. Folate-polyethylene glycol-ultrasmall superparamagnetic iron oxide nanoparticles. 2011 May 9 [Updated 2011 Jul 14]. 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/NBK56365/pdf/Bookshelf_NBK56365.pdf">PDF version of this page</a> (137K)</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="#P1133.Background" ref="log$=inpage&link_id=inpage">Background</a></li><li><a href="#P1133.Synthesis" ref="log$=inpage&link_id=inpage">Synthesis</a></li><li><a href="#P1133.In_Vitro_Studies_Testing_in_Cells" ref="log$=inpage&link_id=inpage"><i>In Vitro</i> Studies: Testing in Cells and Tissues</a></li><li><a href="#P1133.Animal_Studies" ref="log$=inpage&link_id=inpage">Animal Studies</a></li><li><a href="#P1133.Human_Studies" ref="log$=inpage&link_id=inpage">Human Studies</a></li><li><a href="#P1133.References" ref="log$=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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