Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific
Abstract Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nano...
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| Veröffentlicht in: | Nanomedicine 2016-08, Vol.12 (6), p.1535-1542 |
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| creator | McConnell, Heather L., B.S Schwartz, Daniel L., B.A Richardson, Brian E., Ph.D Woltjer, Randall L., M.D., Ph.D Muldoon, Leslie L., Ph.D Neuwelt, Edward A., M.D |
| description | Abstract Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo . We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163+ /CD68+ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic. |
| doi_str_mv | 10.1016/j.nano.2016.03.009 |
| format | Article |
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Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo . We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163+ /CD68+ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.</description><identifier>ISSN: 1549-9634</identifier><identifier>EISSN: 1549-9642</identifier><identifier>DOI: 10.1016/j.nano.2016.03.009</identifier><identifier>PMID: 27071335</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Brain - pathology ; Brain Neoplasms - diagnostic imaging ; Contrast agents ; Contrast Media ; Ferrosoferric Oxide - pharmacokinetics ; Humans ; Internal Medicine ; Iron oxide nanoparticles ; Macrophages ; Magnetic Resonance Imaging ; MRI ; Nanoparticles ; Neuroinflammation ; Rats</subject><ispartof>Nanomedicine, 2016-08, Vol.12 (6), p.1535-1542</ispartof><rights>2016</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c609t-6bbf22392985419ed14755e3d56cd711f99d16ce1ece32dd4933488969cc3fda3</citedby><cites>FETCH-LOGICAL-c609t-6bbf22392985419ed14755e3d56cd711f99d16ce1ece32dd4933488969cc3fda3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1549963416300272$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27071335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McConnell, Heather L., B.S</creatorcontrib><creatorcontrib>Schwartz, Daniel L., B.A</creatorcontrib><creatorcontrib>Richardson, Brian E., Ph.D</creatorcontrib><creatorcontrib>Woltjer, Randall L., M.D., Ph.D</creatorcontrib><creatorcontrib>Muldoon, Leslie L., Ph.D</creatorcontrib><creatorcontrib>Neuwelt, Edward A., M.D</creatorcontrib><title>Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific</title><title>Nanomedicine</title><addtitle>Nanomedicine</addtitle><description>Abstract Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo . We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163+ /CD68+ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.</description><subject>Animals</subject><subject>Brain - pathology</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Contrast agents</subject><subject>Contrast Media</subject><subject>Ferrosoferric Oxide - pharmacokinetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Iron oxide nanoparticles</subject><subject>Macrophages</subject><subject>Magnetic Resonance Imaging</subject><subject>MRI</subject><subject>Nanoparticles</subject><subject>Neuroinflammation</subject><subject>Rats</subject><issn>1549-9634</issn><issn>1549-9642</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk9v1DAQxSMEon_gC3BAOXJJsD2JHUuoEqooRarEgVbiZnntSfE2sYOdVOy3x9GWFe0BcbFH8u89eeZNUbyhpKaE8vfb2msfapbrmkBNiHxWHNO2kZXkDXt-qKE5Kk5S2hICIkMviyMmiKAA7XHx_QLjMoZfuzkM5Wo36Tg7M2C5TLO-w9L5chN1Pu0Snb8ttVlmLD0uMTjfD3oc9eyCL10qDQ5DlSY0rnfmVfGi10PC1w_3aXFz8en6_LK6-vr5y_nHq8pwIueKbzY9YyCZ7NqGSrS0EW2LYFturKC0l9JSbpCiQWDWNhKg6TrJpTHQWw2nxdned1o2I1qDfo56UFN0o447FbRTj1-8-6Fuw71qZNsKRrLBuweDGH4umGY1urS2oj2GJSnagQAKXHb_gZJWcEGgySjboyaGlCL2hx9Rotb01Fat41ZreoqAysFk0du_ezlI_sSVgQ97APNE7x1GlYxDb9C6iGZWNrh_-589kZvBeWf0cIc7TNuwRJ-zUlQlpoj6tu7Puj6UAyFMMPgN5xnCcQ</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>McConnell, Heather L., B.S</creator><creator>Schwartz, Daniel L., B.A</creator><creator>Richardson, Brian E., Ph.D</creator><creator>Woltjer, Randall L., M.D., Ph.D</creator><creator>Muldoon, Leslie L., Ph.D</creator><creator>Neuwelt, Edward A., M.D</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20160801</creationdate><title>Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific</title><author>McConnell, Heather L., B.S ; Schwartz, Daniel L., B.A ; Richardson, Brian E., Ph.D ; Woltjer, Randall L., M.D., Ph.D ; Muldoon, Leslie L., Ph.D ; Neuwelt, Edward A., M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c609t-6bbf22392985419ed14755e3d56cd711f99d16ce1ece32dd4933488969cc3fda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Brain - pathology</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Contrast agents</topic><topic>Contrast Media</topic><topic>Ferrosoferric Oxide - pharmacokinetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Iron oxide nanoparticles</topic><topic>Macrophages</topic><topic>Magnetic Resonance Imaging</topic><topic>MRI</topic><topic>Nanoparticles</topic><topic>Neuroinflammation</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McConnell, Heather L., B.S</creatorcontrib><creatorcontrib>Schwartz, Daniel L., B.A</creatorcontrib><creatorcontrib>Richardson, Brian E., Ph.D</creatorcontrib><creatorcontrib>Woltjer, Randall L., M.D., Ph.D</creatorcontrib><creatorcontrib>Muldoon, Leslie L., Ph.D</creatorcontrib><creatorcontrib>Neuwelt, Edward A., M.D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nanomedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McConnell, Heather L., B.S</au><au>Schwartz, Daniel L., B.A</au><au>Richardson, Brian E., Ph.D</au><au>Woltjer, Randall L., M.D., Ph.D</au><au>Muldoon, Leslie L., Ph.D</au><au>Neuwelt, Edward A., M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific</atitle><jtitle>Nanomedicine</jtitle><addtitle>Nanomedicine</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>12</volume><issue>6</issue><spage>1535</spage><epage>1542</epage><pages>1535-1542</pages><issn>1549-9634</issn><eissn>1549-9642</eissn><abstract>Abstract Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo . We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163+ /CD68+ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27071335</pmid><doi>10.1016/j.nano.2016.03.009</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Brain - pathology Brain Neoplasms - diagnostic imaging Contrast agents Contrast Media Ferrosoferric Oxide - pharmacokinetics Humans Internal Medicine Iron oxide nanoparticles Macrophages Magnetic Resonance Imaging MRI Nanoparticles Neuroinflammation Rats |
| title | Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific |
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