Detection of Lymph Node Involvement in Hematologic Malignancies Using Micromagnetic Resonance Lymphangiography with a Gadolinum-Labeled Dendrimer Nanoparticle
Identifieur interne : 003D76 ( Pmc/Checkpoint ); précédent : 003D75; suivant : 003D77Detection of Lymph Node Involvement in Hematologic Malignancies Using Micromagnetic Resonance Lymphangiography with a Gadolinum-Labeled Dendrimer Nanoparticle
Auteurs : Hisataka Kobayashi [États-Unis] ; Satomi Kawamoto [États-Unis] ; Martin W. Brechbiel [États-Unis] ; Marcelino Bernardo [États-Unis] ; Noriko Sato [États-Unis] ; Thomas A. Waldmann [États-Unis] ; Yutaka Tagaya [États-Unis] ; Peter L. Choyke [États-Unis]Source :
- Neoplasia (New York, N.Y.) [ 1522-8002 ] ; 2005.
Abstract
Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging–based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd)–labeled dendrimer nanoparticle (generation-6; ∼220 kDa/∼10 nm) was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL). Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1–weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C) were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.
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PubMed: 16331884
PubMed Central: 1502021
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<author><name sortKey="Tagaya, Yutaka" sort="Tagaya, Yutaka" uniqKey="Tagaya Y" first="Yutaka" last="Tagaya">Yutaka Tagaya</name>
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<author><name sortKey="Choyke, Peter L" sort="Choyke, Peter L" uniqKey="Choyke P" first="Peter L." last="Choyke">Peter L. Choyke</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Detection of Lymph Node Involvement in Hematologic Malignancies Using Micromagnetic Resonance Lymphangiography with a Gadolinum-Labeled Dendrimer Nanoparticle</title>
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<author><name sortKey="Bernardo, Marcelino" sort="Bernardo, Marcelino" uniqKey="Bernardo M" first="Marcelino" last="Bernardo">Marcelino Bernardo</name>
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<author><name sortKey="Sato, Noriko" sort="Sato, Noriko" uniqKey="Sato N" first="Noriko" last="Sato">Noriko Sato</name>
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<author><name sortKey="Choyke, Peter L" sort="Choyke, Peter L" uniqKey="Choyke P" first="Peter L." last="Choyke">Peter L. Choyke</name>
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<series><title level="j">Neoplasia (New York, N.Y.)</title>
<idno type="ISSN">1522-8002</idno>
<idno type="eISSN">1476-5586</idno>
<imprint><date when="2005">2005</date>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging–based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd)–labeled dendrimer nanoparticle (generation-6; ∼220 kDa/∼10 nm) was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL). Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1–weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C) were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neoplasia</journal-id>
<journal-id journal-id-type="publisher-id">NEO</journal-id>
<journal-title>Neoplasia (New York, N.Y.)</journal-title>
<issn pub-type="ppub">1522-8002</issn>
<issn pub-type="epub">1476-5586</issn>
<publisher><publisher-name>Neoplasia Press, Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">16331884</article-id>
<article-id pub-id-type="pmc">1502021</article-id>
<article-id pub-id-type="publisher-id">05454</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Detection of Lymph Node Involvement in Hematologic Malignancies Using Micromagnetic Resonance Lymphangiography with a Gadolinum-Labeled Dendrimer Nanoparticle</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kobayashi</surname>
<given-names>Hisataka</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kawamoto</surname>
<given-names>Satomi</given-names>
</name>
<xref ref-type="aff" rid="A2">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brechbiel</surname>
<given-names>Martin W.</given-names>
</name>
<xref ref-type="aff" rid="A3">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bernardo</surname>
<given-names>Marcelino</given-names>
</name>
<xref ref-type="aff" rid="A4">§</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sato</surname>
<given-names>Noriko</given-names>
</name>
<xref ref-type="aff" rid="A5">¶</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Waldmann</surname>
<given-names>Thomas A.</given-names>
</name>
<xref ref-type="aff" rid="A5">¶</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tagaya</surname>
<given-names>Yutaka</given-names>
</name>
<xref ref-type="aff" rid="A5">¶</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Choyke</surname>
<given-names>Peter L.</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<aff id="A1"><label>*</label>
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</aff>
<aff id="A2"><label>†</label>
Department of Radiology, School of Medicine, Johns Hopkins University, Bethesda, MD, USA</aff>
<aff id="A3"><label>‡</label>
Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</aff>
<aff id="A4"><label>§</label>
Molecular Imaging Program, Center for Cancer Research, SAIC-Frederick, National Cancer Institute, National Institutes of Health, Frederick, MD, USA</aff>
<aff id="A5"><label>¶</label>
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA</aff>
</contrib-group>
<author-notes><corresp>Address all correspondence to: Hisataka Kobayashi, MD, PhD, Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 1 B40, MSC1088, 10 Center Drive, Bethesda, MD 20892-1088. E-mail: <email>kobayash@mail.nih.gov</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2005</year>
</pub-date>
<volume>7</volume>
<issue>11</issue>
<fpage>984</fpage>
<lpage>991</lpage>
<history><date date-type="received"><day>11</day>
<month>7</month>
<year>2005</year>
</date>
<date date-type="rev-recd"><day>17</day>
<month>8</month>
<year>2005</year>
</date>
<date date-type="accepted"><day>18</day>
<month>8</month>
<year>2005</year>
</date>
</history>
<copyright-statement>Copyright © 2005 Neoplasia Press, Inc. All rights reserved</copyright-statement>
<copyright-year>2005</copyright-year>
<abstract><title>Abstract</title>
<p>Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging–based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd)–labeled dendrimer nanoparticle (generation-6; ∼220 kDa/∼10 nm) was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL). Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1–weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C) were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>Malignant lymphoma</kwd>
<kwd>MRI</kwd>
<kwd>lymph node</kwd>
<kwd>lymphatic flow</kwd>
<kwd>nanoparticle</kwd>
</kwd-group>
<counts><fig-count count="3"></fig-count>
<table-count count="1"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="31"></ref-count>
<page-count count="8"></page-count>
<word-count count="5195"></word-count>
</counts>
</article-meta>
</front>
<floats-wrap><fig id="F1" position="float"><label>Figure 1</label>
<caption><p>Micro-MRL obtained with 3D-FIESTA-C demonstrates better visualization of the normal lymphatic flow than micro-MRL acquired with 3D-fSPGR. MRL images of the upper body of a mouse with 3D-fSPGR (a; animation 1) and 3D-FIESTA-C (b; animation 2), which were serially obtained at 10 minutes postinjection of the G6 contrast agent, are shown from a series of 3D dynamic micro-MR lymphangiograms. 3D-FIESTA-C especially showed the connection of thinner lymphatic vessels (arrows) between lymph nodes better than 3D-fSPGR. Arrowheads indicate injection sites. Broken arrows on (b) indicate the gall bladder.</p>
</caption>
<graphic xlink:href="neo0711-0984-fig001"></graphic>
</fig>
<fig id="F2" position="float"><label>Figure 2</label>
<caption><p>3D-micro-MR lymphangiograms with 3D-FIESTA-C visualized the relationship between the lymphatic system and tumors in mice. Two series of 3D dynamic micro-MR lymphangiograms of mice with Karpas 299 tumors (a and b; animation 3 and 4) and PT-18 tumors (c and d; animations 5 and 6) obtained with repeated 3D-fSPGR (a and c) and 3D-FIESTA-C scans (b and d) at 20 and 25 minutes postinjection of the G6 contrast agent. On micro-MR lymphangiograms with 3D-FIESTA-C, a normal lymphatic system is depicted and is superimposed on Karpas 299 tumors (arrows) (b). In contrast, in a mouse with PT-18, the opacified normal lymphatic tissue fills in around intranodal metastasis (d).</p>
</caption>
<graphic xlink:href="neo0711-0984-fig002a"></graphic>
<graphic xlink:href="neo0711-0984-fig002b"></graphic>
<graphic xlink:href="neo0711-0984-fig002c"></graphic>
<graphic xlink:href="neo0711-0984-fig002d"></graphic>
</fig>
<fig id="F3" position="float"><label>Figure 3</label>
<caption><p>Histologic analyses revealed the growth of PT-18 tumors in lymph nodes, which received lymphatic flow from the primary site. 3D-micro-MR lymphangiograms of axillary lymph nodes in a mouse bearing Karpas 299 tumor (a) and PT-18 metastatic tumors (b and c) are shown with histology (H–E staining, ×20). The axillary lymph nodes in a mouse bearing Karpas 299 tumor are shown in a normal lymph node without metastasis. We noticed this subtle inhomogeneity in all normal lymph nodes possibly because of the location of the lymphatic orifice, from which the contrast agent came into the lymph nodes. This inhomogeneity was clearer in earlier time points and was less clear in later time points. The lymph node tissue with metastatic tumor cells was not enhanced (b). The lymphatic vessels with multilocular cystic dilatation in the lymph node, which were depicted on micro-MRL, were demonstrated by histology (c). The walls of the cystic structures were lined by PT-18 tumor cells.</p>
</caption>
<graphic xlink:href="neo0711-0984-fig003"></graphic>
</fig>
<table-wrap id="T1" position="float"><label>Table 1</label>
<caption><p>Visualization Score of Four Lymph Nodes and Lymphatic Vessels on the Upper Body (<italic>n</italic>
= 7)</p>
</caption>
<table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="2" colspan="1"></th>
<th colspan="4" align="left" rowspan="1">Time (min)<hr></hr>
</th>
</tr>
<tr><th rowspan="1" colspan="1">10</th>
<th rowspan="1" colspan="1">20</th>
<th rowspan="1" colspan="1">30</th>
<th rowspan="1" colspan="1">40</th>
</tr>
<tr><td colspan="4" rowspan="1"><hr></hr>
</td>
</tr>
</thead>
<tbody align="left"><tr><td rowspan="1" colspan="1">3D-fSPGR lymph nodes</td>
<td align="char" char="." rowspan="1" colspan="1">13</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
</tr>
<tr><td rowspan="1" colspan="1">3D-FIESTA-C lymph nodes</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
<td align="char" char="." rowspan="1" colspan="1">14</td>
</tr>
<tr><td rowspan="1" colspan="1">3D-fSPGR lymphatic vessels</td>
<td align="char" char="." rowspan="1" colspan="1">6</td>
<td align="char" char="." rowspan="1" colspan="1">9</td>
<td align="char" char="." rowspan="1" colspan="1">8</td>
<td align="char" char="." rowspan="1" colspan="1">7</td>
</tr>
<tr><td rowspan="1" colspan="1">3D-FIESTA-C lymphatic vessels</td>
<td align="char" char="." rowspan="1" colspan="1">8<xref ref-type="table-fn" rid="TFN1">*</xref>
</td>
<td align="char" char="." rowspan="1" colspan="1">10</td>
<td align="char" char="." rowspan="1" colspan="1">9</td>
<td align="char" char="." rowspan="1" colspan="1">9<xref ref-type="table-fn" rid="TFN1">*</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>Each score is the sum of consensus-based ratings (performed by two readers) for seven mice, with higher scores representing better visualization.</p>
</fn>
<fn id="TFN1"><label>*</label>
<p><italic>P</italic>
< 0.005 compared with 3D-fSPGR.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-wrap>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Kobayashi, Hisataka" sort="Kobayashi, Hisataka" uniqKey="Kobayashi H" first="Hisataka" last="Kobayashi">Hisataka Kobayashi</name>
</noRegion>
<name sortKey="Bernardo, Marcelino" sort="Bernardo, Marcelino" uniqKey="Bernardo M" first="Marcelino" last="Bernardo">Marcelino Bernardo</name>
<name sortKey="Brechbiel, Martin W" sort="Brechbiel, Martin W" uniqKey="Brechbiel M" first="Martin W." last="Brechbiel">Martin W. Brechbiel</name>
<name sortKey="Choyke, Peter L" sort="Choyke, Peter L" uniqKey="Choyke P" first="Peter L." last="Choyke">Peter L. Choyke</name>
<name sortKey="Kawamoto, Satomi" sort="Kawamoto, Satomi" uniqKey="Kawamoto S" first="Satomi" last="Kawamoto">Satomi Kawamoto</name>
<name sortKey="Sato, Noriko" sort="Sato, Noriko" uniqKey="Sato N" first="Noriko" last="Sato">Noriko Sato</name>
<name sortKey="Tagaya, Yutaka" sort="Tagaya, Yutaka" uniqKey="Tagaya Y" first="Yutaka" last="Tagaya">Yutaka Tagaya</name>
<name sortKey="Waldmann, Thomas A" sort="Waldmann, Thomas A" uniqKey="Waldmann T" first="Thomas A." last="Waldmann">Thomas A. Waldmann</name>
</country>
</tree>
</affiliations>
</record>
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