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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging</title>
<author><name sortKey="Emerson, Derek K" sort="Emerson, Derek K" uniqKey="Emerson D" first="Derek K." last="Emerson">Derek K. Emerson</name>
</author>
<author><name sortKey="Limmer, Karl K" sort="Limmer, Karl K" uniqKey="Limmer K" first="Karl K." last="Limmer">Karl K. Limmer</name>
</author>
<author><name sortKey="Hall, David J" sort="Hall, David J" uniqKey="Hall D" first="David J." last="Hall">David J. Hall</name>
</author>
<author><name sortKey="Han, Sung Ho" sort="Han, Sung Ho" uniqKey="Han S" first="Sung-Ho" last="Han">Sung-Ho Han</name>
</author>
<author><name sortKey="Eckelman, William C" sort="Eckelman, William C" uniqKey="Eckelman W" first="William C." last="Eckelman">William C. Eckelman</name>
</author>
<author><name sortKey="Kane, Christopher J" sort="Kane, Christopher J" uniqKey="Kane C" first="Christopher J." last="Kane">Christopher J. Kane</name>
</author>
<author><name sortKey="Wallace, Anne M" sort="Wallace, Anne M" uniqKey="Wallace A" first="Anne M." last="Wallace">Anne M. Wallace</name>
</author>
<author><name sortKey="Vera, David R" sort="Vera, David R" uniqKey="Vera D" first="David R." last="Vera">David R. Vera</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22753678</idno>
<idno type="pmc">3447170</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447170</idno>
<idno type="RBID">PMC:3447170</idno>
<idno type="doi">10.1148/radiol.12120638</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">003182</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003182</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging</title>
<author><name sortKey="Emerson, Derek K" sort="Emerson, Derek K" uniqKey="Emerson D" first="Derek K." last="Emerson">Derek K. Emerson</name>
</author>
<author><name sortKey="Limmer, Karl K" sort="Limmer, Karl K" uniqKey="Limmer K" first="Karl K." last="Limmer">Karl K. Limmer</name>
</author>
<author><name sortKey="Hall, David J" sort="Hall, David J" uniqKey="Hall D" first="David J." last="Hall">David J. Hall</name>
</author>
<author><name sortKey="Han, Sung Ho" sort="Han, Sung Ho" uniqKey="Han S" first="Sung-Ho" last="Han">Sung-Ho Han</name>
</author>
<author><name sortKey="Eckelman, William C" sort="Eckelman, William C" uniqKey="Eckelman W" first="William C." last="Eckelman">William C. Eckelman</name>
</author>
<author><name sortKey="Kane, Christopher J" sort="Kane, Christopher J" uniqKey="Kane C" first="Christopher J." last="Kane">Christopher J. Kane</name>
</author>
<author><name sortKey="Wallace, Anne M" sort="Wallace, Anne M" uniqKey="Wallace A" first="Anne M." last="Wallace">Anne M. Wallace</name>
</author>
<author><name sortKey="Vera, David R" sort="Vera, David R" uniqKey="Vera D" first="David R." last="Vera">David R. Vera</name>
</author>
</analytic>
<series><title level="j">Radiology</title>
<idno type="ISSN">0033-8419</idno>
<idno type="eISSN">1527-1315</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Technetium 99m-labeled cyanine 7 tilmanocept is a multireporter probe that exhibits the in vitro and in vivo requirements for receptor-targeted sentinel lymph node mapping with nuclear and optical imaging.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><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">Radiology</journal-id>
<journal-id journal-id-type="iso-abbrev">Radiology</journal-id>
<journal-id journal-id-type="hwp">radiology</journal-id>
<journal-id journal-id-type="pmc">radiology</journal-id>
<journal-id journal-id-type="publisher-id">Radiology</journal-id>
<journal-title-group><journal-title>Radiology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0033-8419</issn>
<issn pub-type="epub">1527-1315</issn>
<publisher><publisher-name>Radiological Society of North America, Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22753678</article-id>
<article-id pub-id-type="pmc">3447170</article-id>
<article-id pub-id-type="publisher-id">120638</article-id>
<article-id pub-id-type="doi">10.1148/radiol.12120638</article-id>
<article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>26</subject>
</subj-group>
<subj-group subj-group-type="heading"><subject>Original Research</subject>
<subj-group><subject>Molecular Imaging</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Emerson</surname>
<given-names>Derek K.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Limmer</surname>
<given-names>Karl K.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Hall</surname>
<given-names>David J.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Han</surname>
<given-names>Sung-Ho</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Eckelman</surname>
<given-names>William C.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Kane</surname>
<given-names>Christopher J.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Wallace</surname>
<given-names>Anne M.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Vera</surname>
<given-names>David R.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<aff id="aff1">From the Moores UCSD Cancer Center (D.K.E., K.K.L., D.J.H., S.H.H., C.J.K., A.M.W., D.R.V.), Department of Radiology (D.J.H., S.H.H., W.C.E., D.R.V.), Department of Surgery (D.K.E., K.K.L., C.J.K., A.M.W.), and UCSD In Vivo Cancer and Molecular Imaging Center (D.J.H., S.H.H., W.C.E., D.R.V.), University of California, San Diego, 3855 Health Sciences Dr, La Jolla, CA 92093.</aff>
</contrib-group>
<author-notes><corresp id="cor1"><bold>Address correspondence to</bold>
D.R.V. (e-mail: <italic><email>dvera@ucsd.edu</email>
</italic>
).</corresp>
<fn fn-type="con"><p><bold>Author contributions:</bold>
Guarantors of integrity of entire study, D.J.H., A.M.W., D.R.V.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, D.K.E., K.K.L., D.J.H., A.M.W., D.R.V.; experimental studies, D.K.E., K.K.L., D.J.H., A.M.W., D.R.V.; statistical analysis, D.K.E., K.K.L., D.J.H., S.H.H., A.M.W.; and manuscript editing, D.K.E., K.K.L., D.J.H., W.C.E., C.J.K., A.M.W., D.R.V.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>10</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><month>10</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>10</month>
<year>2013</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
. </pmc-comment>
<volume>265</volume>
<issue>1</issue>
<fpage>186</fpage>
<lpage>193</lpage>
<permissions><copyright-statement>© RSNA, 2012</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="120638.pdf"></self-uri>
<abstract abstract-type="precis"><p>Technetium 99m-labeled cyanine 7 tilmanocept is a multireporter probe that exhibits the in vitro and in vivo requirements for receptor-targeted sentinel lymph node mapping with nuclear and optical imaging.</p>
</abstract>
<abstract><sec><title>Purpose:</title>
<p>To determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection.</p>
</sec>
<sec><title>Materials and Methods:</title>
<p>The animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m (<sup>99m</sup>
Tc) -labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of <sup>99m</sup>
Tc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of <sup>99m</sup>
Tc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student <italic>t</italic>
test.</p>
</sec>
<sec><title>Results:</title>
<p>In vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L ± 0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6 × 10<sup>3</sup>
counts · sec<sup>−1</sup>
· μW<sup>−1</sup>
per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (<italic>P</italic>
= .005 to <italic>P</italic>
= .042) in the low-dose group than in the high-dose group; this finding was consistent with receptor-mediated image formation.</p>
</sec>
<sec><title>Conclusion:</title>
<p>The multireporter probe <sup>99m</sup>
Tc-labeled Cy7 tilmanocept exhibits in vitro and in vivo receptor-binding properties for successful receptor-targeted SLN mapping with nuclear and optical imaging.</p>
<p>© RSNA, 2012</p>
<p>Supplemental material: <italic><ext-link ext-link-type="uri" xlink:href="http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120638/-/DC1">http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120638/-/DC1</ext-link>
</italic>
</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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