Serveur d'exploration sur le lymphœdème

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

Identifieur interne : 001B06 ( Pmc/Corpus ); précédent : 001B05; suivant : 001B07

Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

Auteurs : Anne Robe ; Emilie Pic ; Henri-Pierre Lassalle ; Lina Bezdetnaya ; François Guillemin ; Frédéric Marchal

Source :

RBID : PMC:2375898

Abstract

Background

Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the in vivo imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.

Methods

CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. In vivo fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.

Results

QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.

Conclusion

Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.


Url:
DOI: 10.1186/1471-2407-8-111
PubMed: 18430208
PubMed Central: 2375898

Links to Exploration step

PMC:2375898

Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice</title>
<author>
<name sortKey="Robe, Anne" sort="Robe, Anne" uniqKey="Robe A" first="Anne" last="Robe">Anne Robe</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Pic, Emilie" sort="Pic, Emilie" uniqKey="Pic E" first="Emilie" last="Pic">Emilie Pic</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lassalle, Henri Pierre" sort="Lassalle, Henri Pierre" uniqKey="Lassalle H" first="Henri-Pierre" last="Lassalle">Henri-Pierre Lassalle</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bezdetnaya, Lina" sort="Bezdetnaya, Lina" uniqKey="Bezdetnaya L" first="Lina" last="Bezdetnaya">Lina Bezdetnaya</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Guillemin, Francois" sort="Guillemin, Francois" uniqKey="Guillemin F" first="François" last="Guillemin">François Guillemin</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Marchal, Frederic" sort="Marchal, Frederic" uniqKey="Marchal F" first="Frédéric" last="Marchal">Frédéric Marchal</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">18430208</idno>
<idno type="pmc">2375898</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375898</idno>
<idno type="RBID">PMC:2375898</idno>
<idno type="doi">10.1186/1471-2407-8-111</idno>
<date when="2008">2008</date>
<idno type="wicri:Area/Pmc/Corpus">001B06</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B06</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice</title>
<author>
<name sortKey="Robe, Anne" sort="Robe, Anne" uniqKey="Robe A" first="Anne" last="Robe">Anne Robe</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Pic, Emilie" sort="Pic, Emilie" uniqKey="Pic E" first="Emilie" last="Pic">Emilie Pic</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lassalle, Henri Pierre" sort="Lassalle, Henri Pierre" uniqKey="Lassalle H" first="Henri-Pierre" last="Lassalle">Henri-Pierre Lassalle</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bezdetnaya, Lina" sort="Bezdetnaya, Lina" uniqKey="Bezdetnaya L" first="Lina" last="Bezdetnaya">Lina Bezdetnaya</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Guillemin, Francois" sort="Guillemin, Francois" uniqKey="Guillemin F" first="François" last="Guillemin">François Guillemin</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Marchal, Frederic" sort="Marchal, Frederic" uniqKey="Marchal F" first="Frédéric" last="Marchal">Frédéric Marchal</name>
<affiliation>
<nlm:aff id="I1">CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">BMC Cancer</title>
<idno type="eISSN">1471-2407</idno>
<imprint>
<date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the
<italic>in vivo </italic>
imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.</p>
</sec>
<sec sec-type="methods">
<title>Methods</title>
<p>CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye.
<italic>In vivo </italic>
fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.</p>
</sec>
<sec>
<title>Results</title>
<p>QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.</p>
</sec>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">BMC Cancer</journal-id>
<journal-title>BMC Cancer</journal-title>
<issn pub-type="epub">1471-2407</issn>
<publisher>
<publisher-name>BioMed Central</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">18430208</article-id>
<article-id pub-id-type="pmc">2375898</article-id>
<article-id pub-id-type="publisher-id">1471-2407-8-111</article-id>
<article-id pub-id-type="doi">10.1186/1471-2407-8-111</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice</article-title>
</title-group>
<contrib-group>
<contrib id="A1" contrib-type="author">
<name>
<surname>Robe</surname>
<given-names>Anne</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>a.robe@nancy.fnclcc.fr</email>
</contrib>
<contrib id="A2" contrib-type="author">
<name>
<surname>Pic</surname>
<given-names>Emilie</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>e.pic@nancy.fnclcc.fr</email>
</contrib>
<contrib id="A3" contrib-type="author">
<name>
<surname>Lassalle</surname>
<given-names>Henri-Pierre</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>h.lassalle@nancy.fnclcc.fr</email>
</contrib>
<contrib id="A4" contrib-type="author">
<name>
<surname>Bezdetnaya</surname>
<given-names>Lina</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>l.bolotine@nancy.fnclcc.fr</email>
</contrib>
<contrib id="A5" contrib-type="author">
<name>
<surname>Guillemin</surname>
<given-names>François</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>f.guillemin@nancy.fnclcc.fr</email>
</contrib>
<contrib id="A6" corresp="yes" contrib-type="author">
<name>
<surname>Marchal</surname>
<given-names>Frédéric</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>f.marchal@nancy.fnclcc.fr</email>
</contrib>
</contrib-group>
<aff id="I1">
<label>1</label>
CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France</aff>
<pub-date pub-type="collection">
<year>2008</year>
</pub-date>
<pub-date pub-type="epub">
<day>22</day>
<month>4</month>
<year>2008</year>
</pub-date>
<volume>8</volume>
<fpage>111</fpage>
<lpage>111</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.biomedcentral.com/1471-2407/8/111"></ext-link>
<history>
<date date-type="received">
<day>8</day>
<month>9</month>
<year>2007</year>
</date>
<date date-type="accepted">
<day>22</day>
<month>4</month>
<year>2008</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2008 Robe et al; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2008</copyright-year>
<copyright-holder>Robe et al; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0">
<p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0"></ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
<pmc-comment> Robe Anne a.robe@nancy.fnclcc.fr Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice 2008BMC Cancer 8(1): 111-. (2008)1471-2407(2008)8:1<111>urn:ISSN:1471-2407</pmc-comment>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the
<italic>in vivo </italic>
imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.</p>
</sec>
<sec sec-type="methods">
<title>Methods</title>
<p>CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye.
<italic>In vivo </italic>
fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.</p>
</sec>
<sec>
<title>Results</title>
<p>QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.</p>
</sec>
</abstract>
</article-meta>
</front>
<body>
<sec>
<title>Background</title>
<p>Breast cancer is the first cause of cancer death with a 100% rising in incidence from 1980 to 2000 and 35% growth in mortality [
<xref ref-type="bibr" rid="B1">1</xref>
]. Axillary lymph node dissection (ALND) is the standard surgical treatment in breast cancer patients. It consists in whole lymphatic axillary chain removal with the aim to reveal presence of metastases by histology analyses. However, this procedure leads to numerous morbidity problems such as pain, lymphocel, restriction of arm motion, chronic lymphedema, paresthesia, and, as a consequence, deterioration of life quality. For these reasons, an alternative treatment consisting in the sentinel lymph node (SLN) biopsy has been met with enthusiasm by clinicians. The SLN is the first node in the lymphatic basin into which drains the primary tumour [
<xref ref-type="bibr" rid="B2">2</xref>
]. As a result, axillary lymph node status is the most important prognostic factor and a determinant in the choice of therapy [
<xref ref-type="bibr" rid="B3">3</xref>
]. SLN biopsy consists in
<sup>99m</sup>
Tc-radiolabeled sulfur colloid injection the day before surgery in peritumoral or periareolar area [
<xref ref-type="bibr" rid="B4">4</xref>
] followed by lymphoscintigraphy to identify radioactive lymph node(s). During the surgery, a blue dye is injected in the same way and SLN is thus identified as blue and hot lymph node, one of these criterions only is not sufficient for a successful SLN identification [
<xref ref-type="bibr" rid="B5">5</xref>
]. Despite the significant improvement of SLN biopsy over ALDN, the problems related to potential radiation hazards along with an extra cost of the radioisotope, to allergic reactions after blue dye injection and the overall procedure duration are limiting factors for this technique [
<xref ref-type="bibr" rid="B6">6</xref>
]. The ideal method should be sensitive, accurate, rapid, non invasive, non radioactive, and potentially usable in a laparoscopic setting for gastrointestinal tumors [
<xref ref-type="bibr" rid="B7">7</xref>
]. None of the current methods fulfills all of these criteria. Lymphatic mapping with blue dye results in a high rate of false-positive nodes because the small dye particles can readily diffuse through the true SLN and traverse multiple nodes [
<xref ref-type="bibr" rid="B8">8</xref>
]. Additionally, blue dye has poor tissue contrast and is difficult to detect in deep, dark anatomical regions such as the abdomen. Although the use of radioisotope tracers has improved the detection rate and accuracy of SLN mapping, the high radioactivity of the primary injection site can interfere with intraoperative in vivo detection of nearby nodes [
<xref ref-type="bibr" rid="B3">3</xref>
]. Additionally, if radioisotopes are injected during surgery, the time period required for the tracer to migrate to the SLN may delay the operative procedure. Conversely, preoperative injection of the radiocolloid tracer often necessitates anywhere from 2 to 16 hours before surgery. This is difficult, if not impossible, to accomplish and is applicable only in endoscopically accessible regions of the colon and stomach [
<xref ref-type="bibr" rid="B7">7</xref>
].</p>
<p>Quantum dots (QDs) are fluorescent inorganic nanometer sized crystals with remarkable unique optical and electronic properties. They are composed of a fluorescent core of semiconductor heavy metals. In order to limit their potentially toxic effects due to the release of Cd
<sup>2+ </sup>
or Se
<sup>2- </sup>
ions in case of oxidation of the core (by ultraviolet (UV) light or oxygen) and to passivate the defects on its surface, this core is encapsulated in a shell of organic material, polymeric or lipid-based layers then coat the shell. They have a good quantum yield and absorption cross-section such that single QD fluorescence imaging is possible in cells. QDs have been already applied to visualize SLN in gastrointestinal tract [
<xref ref-type="bibr" rid="B7">7</xref>
], pleural space [
<xref ref-type="bibr" rid="B9">9</xref>
], lung area [
<xref ref-type="bibr" rid="B10">10</xref>
], oesophageal area [
<xref ref-type="bibr" rid="B11">11</xref>
], skin [
<xref ref-type="bibr" rid="B12">12</xref>
] and axilla [
<xref ref-type="bibr" rid="B13">13</xref>
] using infrared light. Recently, red and infra-red emitting QDs were imaged in inguinal and axillary lymph nodes in tumor bearing mice already 3 min after local injection [
<xref ref-type="bibr" rid="B14">14</xref>
]. Major difficulty in using QDs
<italic>in vivo </italic>
is their unknown potential toxicity. However, it has been demonstrated that the injection of 2.10
<sup>9 </sup>
QDs/cell in
<italic>xenopus </italic>
embryos unaltered their phenotype and health [
<xref ref-type="bibr" rid="B15">15</xref>
] and that QDs triggered apoptosis via reactive oxygen species (ROS) production only when they are not coated with ZnS [
<xref ref-type="bibr" rid="B16">16</xref>
,
<xref ref-type="bibr" rid="B17">17</xref>
]. QDs toxicity study is ultimately related to the investigation of their biodistribution in pre-clinical models. Currently, only few detailed works on QDs biodistribution in rodents have been realized [
<xref ref-type="bibr" rid="B18">18</xref>
-
<xref ref-type="bibr" rid="B20">20</xref>
].</p>
<p>The primary objective of this work was to detect and quantify at different times after the injection the selective accumulation of carboxyl coated QDs in axillary draining lymph nodes. Secondly, we assessed the biodistribution of QDs in different tissues by fluorescence microscopy and chemical extraction procedures. The rationale for the choice of carboxyl coating was based on the observation that negative charge confine to QDs certain selectivity to reticuloendothelial system (RES) [
<xref ref-type="bibr" rid="B21">21</xref>
] along with the excellent retention in lymph nodes [
<xref ref-type="bibr" rid="B22">22</xref>
]. Red emitting 655 nm QDs were considered in this study because of their better fluorescence quantum yield compared to that of IR QDs (fluorescence quantum yield) allowing better quantification with regard to detection level of spectroscopic tools.</p>
</sec>
<sec sec-type="methods">
<title>Methods</title>
<sec>
<title>Animals</title>
<p>Eight to twelve weeks old female athymic Fox nude mice (Hsd:Athymic Nude-
<italic>Foxn1nu</italic>
) (Harlan, Gannat, France) weighing from 15 to 25 g were used in these experiments. Mice were kept in 12 h light/dark cycle and had access to food and water
<italic>ad libitum </italic>
until 24 h before the experimentation. Starvation was performed 24 h before manipulation because of possible food fluorescence interference at the emission wavelength of the QDs. Animal procedures were performed in compliance with institutional and national guidelines. Six groups of animals, each composed of 5 mice, were used for lymphotropism and biodistribution studies: one control group who received only phosphate buffer saline (PBS), and five experimental groups injected with QDs. All experiments were performed under anesthetic using intraperitoneal injection of 0.01 mL/g of body weight of a solution containing 8 mg/mL ketamine (Ketalar
<sup>®</sup>
, Panpharma, Fougères, France) and 0.8 mg/mL xylazine (Rompun
<sup>®</sup>
, Bayer Pharma, Puteaux, France).</p>
</sec>
<sec>
<title>Quantum Dots and administration</title>
<p>Quantum Dots (QDs) with a maximum emission peaks at 655 nm were purchased from Quantum Dot Corporation (Qdot
<sup>® </sup>
655 ITK™ carboxyl). These QDs are described by the manufacturer as CdSe/ZnS core/shell nanoparticles coated with a polymer having an excess of carboxylic acid groups. Their characteristics include : 16 nm diameter, 94% size monodispersity, extinction coefficient of 800.000 M
<sup>-1 </sup>
cm
<sup>-1 </sup>
at 638 nm, and a fluorescence quantum yield of 80% with a full width at half maximum of 28 nm. Twenty μL of a 1 μM (20 pmol) QDs solution was injected subcutaneously in the distal part of the right anterior paw, together with 20 μL of 1% patent V blue 2.5%
<sup>® </sup>
(Guerbet, Roissy CdG, France) as reference method. The paw was kneaded to allow migration of QDs and blue dye. Mice were sacrificed at 5, 15, 30, 60 min and 24 h after injection by cervical dislocation.</p>
</sec>
<sec>
<title>
<italic>In vivo </italic>
fluorescence spectroscopy</title>
<p>
<italic>In situ </italic>
quantification of fluorescence was carried out using laser-induced fluorescence (LIF) as described previously [
<xref ref-type="bibr" rid="B23">23</xref>
]. Two optical fibers were held in direct contact with the axillary lymph node (ALN). One fiber was coupled to a krypton laser (410 nm) to ensure excitation. The second fiber was coupled to a spectrograph (USB2000, Ocean Optics, Dunedin, FL, USA) and a CCD captor transferred to a PC for a fluorescence spectrum acquisition. The fluorescence of the rhodamine B (1 μM in water) was used for the calibration of the excitation light intensity. Fluorescence measurements were performed at three different sites: on the skin away from injection site (belly skin), on the LN through the skin and after skin removal
<italic>in vivo</italic>
. The measurements were performed at 5, 15, 30, 60 min and 24 h after QDs injection. Measurements in control group were performed at 24 h after PBS injection.</p>
</sec>
<sec>
<title>Fluorescence microscopy</title>
<p>After sacrifice, ALN, bladder, belly skin, spleen, kidney, heart, lung, brain, stomach, liver and intestine were removed and frozen at -80°C. Six micron frozen sections of all organs were prepared after embedding in Tissue Tek
<sup>® </sup>
(Sakura Finetek, Torrance, CA, USA). Fluorescence was observed under an upright epifluorescence microscope (AX-70 Provis, Olympus, Rungis, France) equipped with a 100 W mercury vapor lamp and a Peltier cooled CCD camera (DP50, Olympus). The filter set consisted of a 400–440 nm band pass excitation filter associated with a 570 nm dichroic mirror and a 590 nm long pass filter. Fluorescence images were recorded using × 40 enlargement.</p>
</sec>
<sec>
<title>Quantitative determination of QDs</title>
<p>Organs were removed at time points indicated above, weighed and made soluble in Solvable
<sup>® </sup>
(Perkin-Elmer, Courtaboeuf, France). Solvable
<sup>® </sup>
was added proportionally to organ weight (0.5 mL for a weight ≤ 50 mg, 1.0 mL for a weight ≤ 200 mg and 1.5 mL for a weight ≤ 300 mg). Organs were next incubated at 50°C until the samples become soluble. A sample of each organ, except ALN and bladder, was 40 times diluted in PBS and analyzed by spectrofluorometry (Xenius, SAFAS, Monaco). An excitation wavelength of 350 nm was used and the spectra were collected between 600 and 690 nm. In a parallel set of experiments, a calibration curve for each organ was established while adding a known concentration of QDs to tissue of interest and the fluorescence of the resulting mixture was measured. Blood samples were collected through cardiac puncture in heparinized and cooled tubes 5, 15, 30, 60 min and 24 h after QDs injection. Samples were centrifuged at 3000×g for 10 min at 4°C. Plasma was recovered, ten fold diluted and its fluorescence emission under 450 nm excitation was measured using a spectrofluorometer (PerkinElmer LS50B, Courtaboeuf, France). Urine and feces were collected daily during 2 days. Urine was 10 fold diluted, feces were made soluble by Solvable
<sup>® </sup>
at 50°C and the fluorescence of both samples was measured by spectrofluorometry (PerkinElmer LS50B, Courtaboeuf, France) using a 350 nm excitation wavelength.</p>
</sec>
<sec>
<title>Statistical analyses</title>
<p>The non-parametric test of Kruskall-Wallis was employed to establish statistical significance. Mann-Whitney's U test was subsequently used to compare two by two the groups for which Kruskall-Wallis test was significant. All analyses were performed on StatView
<sup>® </sup>
5.0 software (Abacus concepts, Berkeley, CA, USA) and all results values were expressed by mean ± SEM (standard error of the mean), * for
<italic>P </italic>
< 0.05 and ** for
<italic>P </italic>
< 0.01 compared to the control group.</p>
</sec>
</sec>
<sec>
<title>Results</title>
<sec>
<title>Chemical extraction of QDs in axillary lymph node</title>
<p>Chemical extraction (Figure
<xref ref-type="fig" rid="F1">1</xref>
) of QDs in ALN revealed the presence of 40 ± 12 pmol/g tissue in the ALN already 5 min after injection with a maximum of 209 ± 75 pmol/g at 60 min after injection. Approximately a 4 fold fluorescence decrease was observed 24 h post-injection (47 ± 8 pmol/g) (
<italic>P </italic>
= 0.0088 for all groups). The percentage of migrated QDs (Table
<xref ref-type="table" rid="T1">1</xref>
) has been derived from Figure
<xref ref-type="fig" rid="F1">1</xref>
by calculating the ratio between the quantity of QDs in ALN and the quantity of QDs at the injection (20 pmol). The amount of QDs that migrated to the lymph node 60 min after the injection corresponds to 2.42% of the total injected dose.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption>
<p>Percentage of QDs injected quantity detected in ALN by spectrofluorometry after chemical extraction.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<td align="center">
<bold>5 min</bold>
</td>
<td align="center">
<bold>15 min</bold>
</td>
<td align="center">
<bold>30 min</bold>
</td>
<td align="center">
<bold>60 min</bold>
</td>
<td align="center">
<bold>24 h</bold>
</td>
</tr>
</thead>
<tbody>
<tr>
<td align="center">0.47 ± 0.21% **</td>
<td align="center">0.27 ± 0.10% **</td>
<td align="center">1.00 ± 0.47% **</td>
<td align="center">2.42 ± 0.57% **</td>
<td align="center">1.24 ± 0.34% **</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>20 pmol were injected subcutaneously in the anterior paw of nude mice. After sacrifice at 5 min, 15 min, 30 min, 60 min and 24 h after injection, ALN was removed, solubilized and the fluorescence of the solution was measured and is expressed as a percentage of the injected doze. Values were expressed by mean ± SEM, values marked with asterisk were significantly different from control (
<italic>P </italic>
< 0.01). QDs: Quantum Dots; ALN: Axillary Lymph Node</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="F1">
<label>Figure 1</label>
<caption>
<p>
<bold>Concentration of QDs (pmol/g) detected in ALN. </bold>
20 pmol were injected subcutaneously in the distal part of the right anterior paw of nude mice. Mice were sacrificed at 5, 15, 30, 60 min and 24 h after injection. Concentration of QDs (pmol/g) was detected in ALN by spectrofluorometry after chemical extraction. Error bars represent SEM, values marked with asterisk were significantly different from control (
<italic>P </italic>
< 0.01). ALN: Axillary Lymph Node; QDs: Quantum Dots.</p>
</caption>
<graphic xlink:href="1471-2407-8-111-1"></graphic>
</fig>
</sec>
<sec>
<title>Fluorescence microscopy experiments</title>
<p>Figure
<xref ref-type="fig" rid="F2">2</xref>
displays typical transmission and fluorescence images of lymph nodes frozen sections in control ALN 5 min post-injection. Compared to the background fluorescence, the QDs treated lymph nodes exhibited a distinct fluorescence in the trabecular and medullar sinuses (Figure
<xref ref-type="fig" rid="F2">2</xref>
, panel D). It should be noted that QDs fluorescence detected in other examined organs (brain, bladder, spleen, kidneys, heart, lungs, liver and intestine) was not different (data not shown) from the autofluorescence observed in a control lymph node (Figure
<xref ref-type="fig" rid="F2">2</xref>
, panel B).</p>
<fig position="float" id="F2">
<label>Figure 2</label>
<caption>
<p>
<bold>Transmission and fluorescence microscopy images of ALN frozen sections.</bold>
Nude mice were injected with 20 pmol of QDs or PBS (control) in the distal part of the right anterior paw. Panels A, B: transmission and fluorescence images of ALN control; Panels C, D: transmission and fluorescence images of ALN 5 min after QDs injection (40 × enlargement). ALN: Axillary Lymph Node; QDs: Quantum Dots.</p>
</caption>
<graphic xlink:href="1471-2407-8-111-2"></graphic>
</fig>
</sec>
<sec>
<title>QDs biodistribution in organs</title>
<p>Mice were injected with QDs, sacrificed 24 h after injection, all organs were removed and subjected to chemical extraction. Figure
<xref ref-type="fig" rid="F3">3</xref>
exhibits typical fluorescence spectra of ALN, liver, lungs, spleen and kidneys. Except for the ALN, no fluorescence peak at 655 nm was detected in the samples. Similar results were found for all time points (5, 15, 30, 60 min and 24 h) and all other tested organs, namely brain, bladder, heart, intestine and skin (data not shown). In a parallel set of experiments we have computed the detection limit of the QDs concentration for each organ using the fluorescence calibration curve. The detection limit ranges from 0.72 pmol of QDs per g of tissue for the bladder to 4.2 pmol/g of tissue for the liver (Table
<xref ref-type="table" rid="T2">2</xref>
). This suggests that the QDs signal in each organ is below the detection thresholds. Extraction of the QDs in the urine and feces was also performed at 48 h post-injection and no fluorescence was detected in the sample pointing out that QDs were not excreted from the body.</p>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption>
<p>Detection limit of QDs (pmol/g) in each organ after chemical extraction.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<td align="center">
<bold>Tissue</bold>
</td>
<td align="center">ALN</td>
<td align="center">Liver</td>
<td align="center">Kidneys</td>
<td align="center">Spleen</td>
<td align="center">Lungs</td>
<td align="center">Heart</td>
<td align="center">Intestine</td>
<td align="center">Brain</td>
<td align="center">Bladder</td>
<td align="center">Skin</td>
</tr>
</thead>
<tbody>
<tr>
<td align="center">
<bold>Detection limit (pmol/g)</bold>
</td>
<td align="center">2.49</td>
<td align="center">4.20</td>
<td align="center">2.20</td>
<td align="center">2.76</td>
<td align="center">2.78</td>
<td align="center">3.98</td>
<td align="center">2.67</td>
<td align="center">2.69</td>
<td align="center">0.72</td>
<td align="center">1.77</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>QDs: Quantum Dots; ALN: Axillary Lymph Node</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="F3">
<label>Figure 3</label>
<caption>
<p>
<bold>Normalised fluorescence emission spectra of organs extracts.</bold>
ALN, spleen, kidneys, lungs, liver were chemically solubilised 24 h after subcutaneous injection of 20 pmol of QDs. Fluorescence spectra of the extracts were then recorded. Error bars represent SEM. ALN: Axillary Lymph Node; QDs: Quantum Dots.</p>
</caption>
<graphic xlink:href="1471-2407-8-111-3"></graphic>
</fig>
</sec>
<sec>
<title>Kinetic of QDs accumulation in lymph nodes by LIF</title>
<p>The
<italic>in vivo </italic>
kinetics of the QD accumulation in the lymph nodes were studied using fluorescence measurements performed on the animal with a optical fiber spectrofluorometer. No significant fluorescence difference was found concerning the skin aside from the injection point after QDs administration, suggesting that QDs do not migrate into the skin. While QDs emission in the ALN was not detected across the skin, a clear signal was evidenced after incision of the skin and measurement on the ALN (called ALN
<italic>in vivo</italic>
) (Figure
<xref ref-type="fig" rid="F4">4</xref>
) (
<italic>P </italic>
= 0.0209 for 5, 15, 30 min;
<italic>P </italic>
= 0.0339 for 60 min and
<italic>P </italic>
= 0.0143 for 24 h). A very strong fluorescence signal was observed as early as 5 min post-injection (1.79 ± 0.97).
<italic>In vivo </italic>
measured animals exhibited a persistent fluorescence till 60 min observation (3.78 ± 1.36). Except of 30 min time point, we observed a gradual increase in fluorescence till 60 min. This time point (30 min) is likely suffered from a complexity of optical measurements. A considerable fluorescence decrease was observed at 24 h post-injection (1.40 ± 0.46). Measurements performed at the injection site showed very high intensity peak (
<italic>ca</italic>
. 4000 a.u.) with no marked difference in intensity during observation time, till 24 h (data not shown). This suggested that the majority of the injected quantity remained at the injection site.</p>
<fig position="float" id="F4">
<label>Figure 4</label>
<caption>
<p>
<bold>Normalised 655 nm fluorescence intensity detected by LIF with optical fiber spectrofluorometer.</bold>
20 pmol of QDs or PBS (control mice) were injected subcutaneously in the distal part of the anterior paw of a nude mice. Kinetics of LIF measurements were done on skin after QDs injection, ALN with skin and
<italic>in vivo </italic>
for control, 5 min, 15 min, 30 min, 60 min and 24 h. Error bars represent SEM, values marked with asterisk were significantly different from control (* for
<italic>P </italic>
< 0.05). QDs: Quantum Dots; LIF: Laser-Induced Fluorescence; ALN: Axillary Lymph Node.</p>
</caption>
<graphic xlink:href="1471-2407-8-111-4"></graphic>
</fig>
</sec>
</sec>
<sec>
<title>Discussion</title>
<p>
<italic>In vivo </italic>
biodistribution studies of QDs are sparse and deal mostly with intravenously (IV) injected QDs. The general consensus is that QDs distribution depends on their physicochemical properties and in particular, size and coating. Tracer particle size has an important effect on migration time in SLN mapping. Particles < 5 nm diffuse into blood, those between 5 to 10 nm can migrate through nodal tissue and result in false-positive results, and those > 1000 nm largely remain at the injection site. Consequently, we choose QDs with a diameter of 16 nm, since a size range between 15 and 20 nm is optimal to enable the QDs to travel through the lymph channels and be trapped by SLN [
<xref ref-type="bibr" rid="B9">9</xref>
,
<xref ref-type="bibr" rid="B12">12</xref>
]. Concerning coating, we choose carboxyl coated QDs. The carboxyl groups present the property to be negatively charged and therefore display rapid uptake in lymphatics and excellent retention in lymph nodes [
<xref ref-type="bibr" rid="B12">12</xref>
,
<xref ref-type="bibr" rid="B21">21</xref>
,
<xref ref-type="bibr" rid="B24">24</xref>
].</p>
<p>To our knowledge, a single biodistribution study was carried out after non-IV administration of QDs. Gopee
<italic>et al</italic>
. [
<xref ref-type="bibr" rid="B19">19</xref>
] investigated the distribution in healthy mice of 48 pmol intradermally (ID) injected QDs with a diameter of 37 nm and PEG coating. The authors did not find any QDs in lymph nodes until 12 h after injection, whereas we could detect them already 5 minutes following the injection (Figure
<xref ref-type="fig" rid="F1">1</xref>
). An early detection (3 min) of QDs traveling toward inguinal nodes was observed after intratumoral injection of red emitting QDs at concentrations similar to ours [
<xref ref-type="bibr" rid="B14">14</xref>
]. However this observation was not followed by biodistribution investigations. QDs Fluorescence increases with time to reach a maximum at 60 min after the injection. The calculated percentages of the injected dose (2.42% at 60 min and 1.24% at 24 h) (Table
<xref ref-type="table" rid="T1">1</xref>
) were comparable with those of Kim
<italic>et al</italic>
. [
<xref ref-type="bibr" rid="B13">13</xref>
] and Gopee
<italic>et al</italic>
. [
<xref ref-type="bibr" rid="B19">19</xref>
] who found 2–4% and 1.07% respectively in the SLN. We observed a 4 fold decrease of QDs concentration in ALN from 60 min to 24 h post-injection (Figure
<xref ref-type="fig" rid="F1">1</xref>
). We also noted a strong fluorescence of QDs at the injection site. This observation is consistent with the study of Gopee and co-workers [
<xref ref-type="bibr" rid="B19">19</xref>
] who found 60% of cadmium retention at the injection site. We further undertook the study of the biodistribution of QDs in the organs. No fluorescence peak was observed after chemical extraction of Qdot
<sup>® </sup>
655 ITK™ carboxyl in liver, kidneys, spleen, lungs, heart, intestine, brain, bladder, and skin (Figure
<xref ref-type="fig" rid="F3">3</xref>
). This points out that we are below the calculated concentration limit (Table
<xref ref-type="table" rid="T2">2</xref>
), even if the latter is as low as around 2.5 pmol/g of tissue. The lower detection threshold observed for pigmented organs such as liver and heart was expected (Table
<xref ref-type="table" rid="T2">2</xref>
) since the fluorescence detection method employed in our study is very sensitive to the absorption properties of the sample. In contrast to our results, the previous QDs biodistribution studies all evidenced the presence of QDs in the liver and also to a minor extent in spleen and kidneys [
<xref ref-type="bibr" rid="B18">18</xref>
,
<xref ref-type="bibr" rid="B19">19</xref>
]. The plausible explanation could be provided by the difference in the site of injection. Gopee
<italic>et al</italic>
. [
<xref ref-type="bibr" rid="B19">19</xref>
] injected QDs ID in the dorsal flank and found 24 h after injection 6.40% of the initial dose in liver and a small amount in kidneys (0.51%) and spleen (0.18%). We have administrated QDs subcutaneously in the paw. ID injection of QDs in the flank drains differently from the SC injected QDs [
<xref ref-type="bibr" rid="B25">25</xref>
] because of the anatomical differences in lymphatic network of the two regions. Likewise, when intradermal injection is performed on the back, direct lymphatic drainage to retroperitoneal and paravertebral nodes can occur before the injected product is distributed throughout the body [
<xref ref-type="bibr" rid="B26">26</xref>
]. When injection is performed in the paw, the first lymph node that receives direct lymphatic drainage is always in the axillary area. QDs are unlikely to be excreted from the body, neither by urine nor by feces in the time span of 48 h. This observation is in agreement with previous work [
<xref ref-type="bibr" rid="B18">18</xref>
] demonstrating the absence of QDs in urine and feces during ten days. Theses results are explained by the dramatic reduction of renal filtration for QDs with a hydrodynamic diameter higher than 3.5 nm and with negative charges [
<xref ref-type="bibr" rid="B27">27</xref>
]. Taken as a whole, the decline in QDs concentration 24 h post-injection could not be attributed to the elimination and/or migration of QDs to different organs. Assuming very strong retention in SLN, we hypothesize that QDs may diffuse in the second lymph node of the chain. This supposition is consistent with the fluorescence distribution pattern of QDs in SLN (Figure
<xref ref-type="fig" rid="F2">2</xref>
). Indeed QDs fluorescence is extended till medulla sinus, thus rending possible the migration to the distal lymph node through the lymph channels. The interaction of QDs with serum should also be addressed. We did not perform studies on the interaction of carboxyl QDs with serum proteins, however, as it was shown recently anionic or cationic charged QDs were associated with an increase of the hydrodynamic diameter after incubation with serum [
<xref ref-type="bibr" rid="B20">20</xref>
]. Moreover, the intensity of fluorescence of QDs increases in the presence of BSA [
<xref ref-type="bibr" rid="B28">28</xref>
] or hemoglobin [
<xref ref-type="bibr" rid="B29">29</xref>
].</p>
<p>Spectrofluorometry using an optical fiber is a non-invasive procedure for the detection of fluorescent tracers. The results of our study demonstrate that despite the incapacity to detect QDs directly through the skin, LIF measurements allow the detection of QDs in ALN after skin incision with a profile similar to chemical extraction (Figure
<xref ref-type="fig" rid="F4">4</xref>
). However, non-invasive measurements are frequently suffering from significant variations of measurements, related to light diffusion and scattering. Further, actually, our work is a preliminary step to use of NIR emitting QDs which we expect the detection of QDs through the skin without any incision. In the future, the non-invasive measurements could be achieved by modulating an excitation wavelength and using NIR emitting QDs. The excitation wavelength in our study was set to 410 nm. Using an excitation at larger wavelengths should result in less skin absorption and scattering, and should make deep tissue imaging possible. Detection of QDs with optical fiber spectroscopy opens perspectives for the utilization of this technique in operation theatre, since it can provide a rapid and reliable QDs detection immediately after SLN excision. A limitation to the clinical use of QDs for SLN mapping is their potential toxicity [
<xref ref-type="bibr" rid="B30">30</xref>
]. However, because most of the injected dose is eliminated by removal of the injection site and nodal tissue, the eventual toxicity may be negligible. Furthermore, to avoid toxicity caused by biodegradation of QDs and exposition of core metal ions, QDs with non-heavy metal cores (such as indium) would be developed along with ameliorations of surface chemistry [
<xref ref-type="bibr" rid="B31">31</xref>
].</p>
</sec>
<sec>
<title>Conclusion</title>
<p>In this study we demonstrated that 655 nm emitting QDs with carboxyl coating allow the visualization of axillary draining lymph node (ALN) after subcutaneous injection of a very weak quantity of QDs (20 pmol). Unlike other tracers, QDs rapidly localize to and remain trapped in the SLN. A strong fluorescence signal is obtained within a few minutes lasting at least 24 h as measured with optical fiber spectrofluorometry, a minimally invasive technique allowing rapid pre-operative complete procedure. Fluorescence microscopy and chemical extraction confirmed highly selective QDs accumulation in the ALN corresponding to 2.42% of the injected dose at 60 min after the injection; the major part remaining at injection site. This rapid and selective accumulation of QDs in ALN together with the eventual non-invasive fluorescence detection offers an exciting opportunity to track lymphatic flow in real time and guide their nodal dissection after one simple intraoperative injection.</p>
</sec>
<sec>
<title>List of abbreviations</title>
<p>au: arbitrary unit; ALN: Axillary Lymph Node; ALND: Axillary Lymph Node Dissection; ICP-AES: Inductive Coupled Plasma Atomic Emission Spectroscopy; ID: Intradermally; IR: Infra-Red; IV: Intravenously; LIF: Laser-Induced Fluorescence; MUA: Mercaptoundecanoic acid; NIR: Near-infrared; PBS: Phosphate Buffer Saline; QD: Quantum Dots; RES: Reticuloendothelial System; ROS: Reactive Oxygen Species; SC: Subcutaneously; SEM: Standard Error of the Mean; SLN: Sentinel Lymph Node; UV: Ultra-Violet.</p>
</sec>
<sec>
<title>Competing interests</title>
<p>The author(s) declares that they have no competing interests.</p>
</sec>
<sec>
<title>Authors' contributions</title>
<p>AR and EP carried out the experimental and mouse studies. AR and EP participated in the pathological studies and performed the statistical analysis. AR, LB, FG and FM participated in the design and coordination of the study. AR, HPL, LB and FM drafted the manuscript. All authors read and approved the final manuscript.</p>
</sec>
<sec>
<title>Pre-publication history</title>
<p>The pre-publication history for this paper can be accessed here:</p>
<p>
<ext-link ext-link-type="uri" xlink:href="http://www.biomedcentral.com/1471-2407/8/111/prepub"></ext-link>
</p>
</sec>
</body>
<back>
<ack>
<sec>
<title>Acknowledgements</title>
<p>The authors would like to thank Mr Benoit Dubertret for proofreading the manuscript.</p>
<p>We thank too A Leroux for advice on pathology, and MA D'Hallewin for critical reading of the manuscript. We acknowledge financial support from Institut National du Cancer (INCA), Comité départemental (54, 55) de la Ligue Nationale de Lutte contre le Cancer, and the Ligue Nationale de Lutte contre le Cancer.</p>
</sec>
</ack>
<ref-list>
<ref id="B1">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Remontet</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Esteve</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Bouvier</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Grosclaude</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Launoy</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Menegoz</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Exbrayat</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Tretare</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Carli</surname>
<given-names>PM</given-names>
</name>
<name>
<surname>Guizard</surname>
<given-names>AV</given-names>
</name>
<name>
<surname>Troussard</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Bercelli</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Colonna</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Halna</surname>
<given-names>JM</given-names>
</name>
<name>
<surname>Hedelin</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Mace-Lesec'h</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Peng</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Buemi</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Velten</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Jougla</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Arveux</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Le Bodic</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Michel</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Sauvage</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Schvartz</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Faivre</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Cancer incidence and mortality in France over the period 1978-2000</article-title>
<source>Rev Epidemiol Sante Publique</source>
<year>2003</year>
<volume>51</volume>
<fpage>3</fpage>
<lpage>30</lpage>
<pub-id pub-id-type="pmid">12684578</pub-id>
</citation>
</ref>
<ref id="B2">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jakub</surname>
<given-names>JW</given-names>
</name>
<name>
<surname>Pendas</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Reintgen</surname>
<given-names>DS</given-names>
</name>
</person-group>
<article-title>Current status of sentinel lymph node mapping and biopsy: facts and controversies</article-title>
<source>Oncologist</source>
<year>2003</year>
<volume>8</volume>
<fpage>59</fpage>
<lpage>68</lpage>
<pub-id pub-id-type="pmid">12604732</pub-id>
<pub-id pub-id-type="doi">10.1634/theoncologist.8-1-59</pub-id>
</citation>
</ref>
<ref id="B3">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Marchal</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Rauch</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Morel</surname>
<given-names>O</given-names>
</name>
<name>
<surname>Mayer</surname>
<given-names>JC</given-names>
</name>
<name>
<surname>Olivier</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Leroux</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Verhaeghe</surname>
<given-names>JL</given-names>
</name>
<name>
<surname>Guillemin</surname>
<given-names>F</given-names>
</name>
</person-group>
<article-title>Results of preoperative lymphoscintigraphy for breast cancer are predictive of identification of axillary sentinel lymph nodes</article-title>
<source>World J Surg</source>
<year>2006</year>
<volume>30</volume>
<fpage>55</fpage>
<lpage>62</lpage>
<pub-id pub-id-type="pmid">16369717</pub-id>
<pub-id pub-id-type="doi">10.1007/s00268-005-0145-3</pub-id>
</citation>
</ref>
<ref id="B4">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>D'Eredita</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Giardina</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Guerrieri</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Berardi</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>A further validation of subareolar injection technique for breast sentinel lymph node biopsy</article-title>
<source>Ann Surg Oncol</source>
<year>2006</year>
<volume>13</volume>
<fpage>701</fpage>
<lpage>707</lpage>
<pub-id pub-id-type="pmid">16523366</pub-id>
<pub-id pub-id-type="doi">10.1245/ASO.2006.04.027</pub-id>
</citation>
</ref>
<ref id="B5">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wilke</surname>
<given-names>LG</given-names>
</name>
<name>
<surname>McCall</surname>
<given-names>LM</given-names>
</name>
<name>
<surname>Posther</surname>
<given-names>KE</given-names>
</name>
<name>
<surname>Whitworth</surname>
<given-names>PW</given-names>
</name>
<name>
<surname>Reintgen</surname>
<given-names>DS</given-names>
</name>
<name>
<surname>Leitch</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Gabram</surname>
<given-names>SG</given-names>
</name>
<name>
<surname>Lucci</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Cox</surname>
<given-names>CE</given-names>
</name>
<name>
<surname>Hunt</surname>
<given-names>KK</given-names>
</name>
<name>
<surname>Herndon</surname>
<given-names>JE</given-names>
<suffix>2nd</suffix>
</name>
<name>
<surname>Giuliano</surname>
<given-names>AE</given-names>
</name>
</person-group>
<article-title>Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial</article-title>
<source>Ann Surg Oncol</source>
<year>2006</year>
<volume>13</volume>
<fpage>491</fpage>
<lpage>500</lpage>
<pub-id pub-id-type="pmid">16514477</pub-id>
<pub-id pub-id-type="doi">10.1245/ASO.2006.05.013</pub-id>
</citation>
</ref>
<ref id="B6">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sato</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Current technical overviews of sentinel lymph node biopsy for breast cancer</article-title>
<source>Breast Cancer</source>
<year>2007</year>
<volume>14</volume>
<fpage>354</fpage>
<lpage>361</lpage>
<pub-id pub-id-type="pmid">17986800</pub-id>
<pub-id pub-id-type="doi">10.2325/jbcs.14.354</pub-id>
</citation>
</ref>
<ref id="B7">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Soltesz</surname>
<given-names>EG</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>SW</given-names>
</name>
<name>
<surname>Laurence</surname>
<given-names>RG</given-names>
</name>
<name>
<surname>De Grand</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Parungo</surname>
<given-names>CP</given-names>
</name>
<name>
<surname>Cohn</surname>
<given-names>LH</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Sentinel lymph node mapping of the gastrointestinal tract by using invisible light</article-title>
<source>Ann Surg Oncol</source>
<year>2006</year>
<volume>13</volume>
<fpage>386</fpage>
<lpage>396</lpage>
<pub-id pub-id-type="pmid">16485157</pub-id>
<pub-id pub-id-type="doi">10.1245/ASO.2006.04.025</pub-id>
</citation>
</ref>
<ref id="B8">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kaleya</surname>
<given-names>RN</given-names>
</name>
<name>
<surname>Heckman</surname>
<given-names>JT</given-names>
</name>
<name>
<surname>Most</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Zager</surname>
<given-names>JS</given-names>
</name>
</person-group>
<article-title>Lymphatic mapping and sentinel node biopsy: a surgical perspective</article-title>
<source>Semin Nucl Med</source>
<year>2005</year>
<volume>35</volume>
<fpage>129</fpage>
<lpage>134</lpage>
<pub-id pub-id-type="pmid">15765375</pub-id>
<pub-id pub-id-type="doi">10.1053/j.semnuclmed.2004.11.004</pub-id>
</citation>
</ref>
<ref id="B9">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Parungo</surname>
<given-names>CP</given-names>
</name>
<name>
<surname>Colson</surname>
<given-names>YL</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>SW</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Cohn</surname>
<given-names>LH</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Sentinel lymph node mapping of the pleural space</article-title>
<source>Chest</source>
<year>2005</year>
<volume>127</volume>
<fpage>1799</fpage>
<lpage>1804</lpage>
<pub-id pub-id-type="pmid">15888861</pub-id>
<pub-id pub-id-type="doi">10.1378/chest.127.5.1799</pub-id>
</citation>
</ref>
<ref id="B10">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Soltesz</surname>
<given-names>EG</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Laurence</surname>
<given-names>RG</given-names>
</name>
<name>
<surname>DeGrand</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Parungo</surname>
<given-names>CP</given-names>
</name>
<name>
<surname>Dor</surname>
<given-names>DM</given-names>
</name>
<name>
<surname>Cohn</surname>
<given-names>LH</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
<name>
<surname>Mihaljevic</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots</article-title>
<source>Ann Thorac Surg</source>
<year>2005</year>
<volume>79</volume>
<fpage>269</fpage>
<lpage>77; discussion 269-77</lpage>
<pub-id pub-id-type="pmid">15620956</pub-id>
<pub-id pub-id-type="doi">10.1016/j.athoracsur.2004.06.055</pub-id>
</citation>
</ref>
<ref id="B11">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Parungo</surname>
<given-names>CP</given-names>
</name>
<name>
<surname>Ohnishi</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>SW</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Laurence</surname>
<given-names>RG</given-names>
</name>
<name>
<surname>Soltesz</surname>
<given-names>EG</given-names>
</name>
<name>
<surname>Chen</surname>
<given-names>FY</given-names>
</name>
<name>
<surname>Colson</surname>
<given-names>YL</given-names>
</name>
<name>
<surname>Cohn</surname>
<given-names>LH</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging</article-title>
<source>J Thorac Cardiovasc Surg</source>
<year>2005</year>
<volume>129</volume>
<fpage>844</fpage>
<lpage>850</lpage>
<pub-id pub-id-type="pmid">15821653</pub-id>
<pub-id pub-id-type="doi">10.1016/j.jtcvs.2004.08.001</pub-id>
</citation>
</ref>
<ref id="B12">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tanaka</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Choi</surname>
<given-names>HS</given-names>
</name>
<name>
<surname>Fujii</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Image-guided oncologic surgery using invisible light: completed pre-clinical development for sentinel lymph node mapping</article-title>
<source>Ann Surg Oncol</source>
<year>2006</year>
<volume>13</volume>
<fpage>1671</fpage>
<lpage>1681</lpage>
<pub-id pub-id-type="pmid">17009138</pub-id>
<pub-id pub-id-type="doi">10.1245/s10434-006-9194-6</pub-id>
</citation>
</ref>
<ref id="B13">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kim</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Lim</surname>
<given-names>YT</given-names>
</name>
<name>
<surname>Soltesz</surname>
<given-names>EG</given-names>
</name>
<name>
<surname>De Grand</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Lee</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Nakayama</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Parker</surname>
<given-names>JA</given-names>
</name>
<name>
<surname>Mihaljevic</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Laurence</surname>
<given-names>RG</given-names>
</name>
<name>
<surname>Dor</surname>
<given-names>DM</given-names>
</name>
<name>
<surname>Cohn</surname>
<given-names>LH</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping</article-title>
<source>Nat Biotechnol</source>
<year>2004</year>
<volume>22</volume>
<fpage>93</fpage>
<lpage>97</lpage>
<pub-id pub-id-type="pmid">14661026</pub-id>
<pub-id pub-id-type="doi">10.1038/nbt920</pub-id>
</citation>
</ref>
<ref id="B14">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ballou</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Ernst</surname>
<given-names>LA</given-names>
</name>
<name>
<surname>Andreko</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Harper</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Fitzpatrick</surname>
<given-names>JA</given-names>
</name>
<name>
<surname>Waggoner</surname>
<given-names>AS</given-names>
</name>
<name>
<surname>Bruchez</surname>
<given-names>MP</given-names>
</name>
</person-group>
<article-title>Sentinel Lymph Node Imaging Using Quantum Dots in Mouse Tumor Models</article-title>
<source>Bioconjug Chem</source>
<year>2007</year>
<pub-id pub-id-type="pmid">17263568</pub-id>
</citation>
</ref>
<ref id="B15">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Dubertret</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Skourides</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Norris</surname>
<given-names>DJ</given-names>
</name>
<name>
<surname>Noireaux</surname>
<given-names>V</given-names>
</name>
<name>
<surname>Brivanlou</surname>
<given-names>AH</given-names>
</name>
<name>
<surname>Libchaber</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>In vivo imaging of quantum dots encapsulated in phospholipid micelles</article-title>
<source>Science</source>
<year>2002</year>
<volume>298</volume>
<fpage>1759</fpage>
<lpage>1762</lpage>
<pub-id pub-id-type="pmid">12459582</pub-id>
<pub-id pub-id-type="doi">10.1126/science.1077194</pub-id>
</citation>
</ref>
<ref id="B16">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chan</surname>
<given-names>WH</given-names>
</name>
<name>
<surname>Shiao</surname>
<given-names>NH</given-names>
</name>
<name>
<surname>Lu</surname>
<given-names>PZ</given-names>
</name>
</person-group>
<article-title>CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals</article-title>
<source>Toxicol Lett</source>
<year>2006</year>
<volume>167</volume>
<fpage>191</fpage>
<lpage>200</lpage>
<pub-id pub-id-type="pmid">17049762</pub-id>
<pub-id pub-id-type="doi">10.1016/j.toxlet.2006.09.007</pub-id>
</citation>
</ref>
<ref id="B17">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cho</surname>
<given-names>SJ</given-names>
</name>
<name>
<surname>Maysinger</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Jain</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Roder</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Hackbarth</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Winnik</surname>
<given-names>FM</given-names>
</name>
</person-group>
<article-title>Long-term exposure to CdTe quantum dots causes functional impairments in live cells</article-title>
<source>Langmuir</source>
<year>2007</year>
<volume>23</volume>
<fpage>1974</fpage>
<lpage>1980</lpage>
<pub-id pub-id-type="pmid">17279683</pub-id>
<pub-id pub-id-type="doi">10.1021/la060093j</pub-id>
</citation>
</ref>
<ref id="B18">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Fischer</surname>
<given-names>HC</given-names>
</name>
<name>
<surname>Liu</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Pang</surname>
<given-names>KS</given-names>
</name>
<name>
<surname>Chan</surname>
<given-names>WCW</given-names>
</name>
</person-group>
<article-title>Pharmacokinetics of nanoscale quantum dots: in vivo distribution, sequestration, and clearance in the rat</article-title>
<source>Advanced Functional Materials</source>
<year>2006</year>
<volume>16</volume>
<fpage>1299</fpage>
<lpage>1305</lpage>
<pub-id pub-id-type="doi">10.1002/adfm.200500529</pub-id>
</citation>
</ref>
<ref id="B19">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gopee</surname>
<given-names>NV</given-names>
</name>
<name>
<surname>Roberts</surname>
<given-names>DW</given-names>
</name>
<name>
<surname>Webb</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Cozart</surname>
<given-names>CR</given-names>
</name>
<name>
<surname>Siitonen</surname>
<given-names>PH</given-names>
</name>
<name>
<surname>Warbritton</surname>
<given-names>AR</given-names>
</name>
<name>
<surname>Yu</surname>
<given-names>WW</given-names>
</name>
<name>
<surname>Colvin</surname>
<given-names>VL</given-names>
</name>
<name>
<surname>Walker</surname>
<given-names>NJ</given-names>
</name>
<name>
<surname>Howard</surname>
<given-names>PC</given-names>
</name>
</person-group>
<article-title>Migration of Intradermally Injected Quantum Dots to Sentinel Organs in Mice</article-title>
<source>Toxicol Sci</source>
<year>2007</year>
<pub-id pub-id-type="pmid">17404394</pub-id>
</citation>
</ref>
<ref id="B20">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Choi</surname>
<given-names>HS</given-names>
</name>
<name>
<surname>Liu</surname>
<given-names>W</given-names>
</name>
<name>
<surname>Misra</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Tanaka</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Zimmer</surname>
<given-names>JP</given-names>
</name>
<name>
<surname>Itty Ipe</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Renal clearance of quantum dots</article-title>
<source>Nat Biotechnol</source>
<year>2007</year>
<volume>25</volume>
<fpage>1165</fpage>
<lpage>1170</lpage>
<pub-id pub-id-type="pmid">17891134</pub-id>
<pub-id pub-id-type="doi">10.1038/nbt1340</pub-id>
</citation>
</ref>
<ref id="B21">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gao</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Cui</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Levenson</surname>
<given-names>RM</given-names>
</name>
<name>
<surname>Chung</surname>
<given-names>LW</given-names>
</name>
<name>
<surname>Nie</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>In vivo cancer targeting and imaging with semiconductor quantum dots</article-title>
<source>Nat Biotechnol</source>
<year>2004</year>
<volume>22</volume>
<fpage>969</fpage>
<lpage>976</lpage>
<pub-id pub-id-type="pmid">15258594</pub-id>
<pub-id pub-id-type="doi">10.1038/nbt994</pub-id>
</citation>
</ref>
<ref id="B22">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>SW</given-names>
</name>
<name>
<surname>Ohnishi</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Kim</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Bawendi</surname>
<given-names>MG</given-names>
</name>
</person-group>
<article-title>Sentinel Lymph Node Mapping With Type-II Quantum Dots</article-title>
<source>Methods Mol Biol</source>
<year>2007</year>
<volume>374</volume>
<fpage>147</fpage>
<lpage>160</lpage>
<pub-id pub-id-type="pmid">17237537</pub-id>
</citation>
</ref>
<ref id="B23">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kamuhabwa</surname>
<given-names>AA</given-names>
</name>
<name>
<surname>Cosserat-Gerardin</surname>
<given-names>I</given-names>
</name>
<name>
<surname>Didelon</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Notter</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Guillemin</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Roskams</surname>
<given-names>T</given-names>
</name>
<name>
<surname>D'Hallewin</surname>
<given-names>MA</given-names>
</name>
<name>
<surname>Baert</surname>
<given-names>L</given-names>
</name>
<name>
<surname>de Witte</surname>
<given-names>PA</given-names>
</name>
</person-group>
<article-title>Biodistribution of hypericin in orthotopic transitional cell carcinoma bladder tumors: implication for whole bladder wall photodynamic therapy</article-title>
<source>Int J Cancer</source>
<year>2002</year>
<volume>97</volume>
<fpage>253</fpage>
<lpage>260</lpage>
<pub-id pub-id-type="pmid">11774272</pub-id>
<pub-id pub-id-type="doi">10.1002/ijc.1594</pub-id>
</citation>
</ref>
<ref id="B24">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hawley</surname>
<given-names>AE</given-names>
</name>
<name>
<surname>Davis</surname>
<given-names>SS</given-names>
</name>
<name>
<surname>Illum</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>Targeting of colloids to lymph nodes: influence of lymphatic physiology and colloidal characteristics</article-title>
<source>Advanced Drug Delivery Reviews</source>
<year>1995</year>
<volume>17</volume>
<fpage>129</fpage>
<lpage>148</lpage>
<pub-id pub-id-type="doi">10.1016/0169-409X(95)00045-9</pub-id>
</citation>
</ref>
<ref id="B25">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kersey</surname>
<given-names>TW</given-names>
</name>
<name>
<surname>Van Eyk</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Lannin</surname>
<given-names>DR</given-names>
</name>
<name>
<surname>Chua</surname>
<given-names>AN</given-names>
</name>
<name>
<surname>Tafra</surname>
<given-names>L</given-names>
</name>
</person-group>
<article-title>Comparison of intradermal and subcutaneous injections in lymphatic mapping</article-title>
<source>J Surg Res</source>
<year>2001</year>
<volume>96</volume>
<fpage>255</fpage>
<lpage>259</lpage>
<pub-id pub-id-type="pmid">11266281</pub-id>
<pub-id pub-id-type="doi">10.1006/jsre.2000.6075</pub-id>
</citation>
</ref>
<ref id="B26">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Uren</surname>
<given-names>RF</given-names>
</name>
</person-group>
<article-title>Lymphatic drainage of the skin</article-title>
<source>Ann Surg Oncol</source>
<year>2004</year>
<volume>11</volume>
<fpage>179S</fpage>
<lpage>85S</lpage>
<pub-id pub-id-type="pmid">15023748</pub-id>
</citation>
</ref>
<ref id="B27">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Frangioni</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>In vivo near-infrared fluorescence imaging</article-title>
<source>Curr Opin Chem Biol</source>
<year>2003</year>
<volume>7</volume>
<fpage>626</fpage>
<lpage>634</lpage>
<pub-id pub-id-type="pmid">14580568</pub-id>
<pub-id pub-id-type="doi">10.1016/j.cbpa.2003.08.007</pub-id>
</citation>
</ref>
<ref id="B28">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yu</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Lai</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Zheng</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Wu</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Long</surname>
<given-names>Z</given-names>
</name>
<name>
<surname>Liang</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Synthesis of functionalized CdTe/CdS QDs for spectrofluorimetric detection of BSA</article-title>
<source>Spectrochim Acta A Mol Biomol Spectrosc</source>
<year>2007</year>
<volume>68</volume>
<fpage>1356</fpage>
<lpage>1361</lpage>
<pub-id pub-id-type="pmid">17482866</pub-id>
<pub-id pub-id-type="doi">10.1016/j.saa.2007.02.016</pub-id>
</citation>
</ref>
<ref id="B29">
<citation citation-type="other">
<person-group person-group-type="author">
<name>
<surname>Hu</surname>
<given-names>DH</given-names>
</name>
<name>
<surname>Wu</surname>
<given-names>HM</given-names>
</name>
<name>
<surname>Liang</surname>
<given-names>JG</given-names>
</name>
<name>
<surname>Han</surname>
<given-names>HY</given-names>
</name>
</person-group>
<article-title>Study on the interaction between CdSe quantum dots and hemoglobin</article-title>
<source>Spectrochim Acta A Mol Biomol Spectrosc</source>
<year>2007</year>
</citation>
</ref>
<ref id="B30">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lin</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Xie</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Patel</surname>
<given-names>MR</given-names>
</name>
<name>
<surname>Yang</surname>
<given-names>YH</given-names>
</name>
<name>
<surname>Li</surname>
<given-names>Z</given-names>
</name>
<name>
<surname>Cao</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Gheysens</surname>
<given-names>O</given-names>
</name>
<name>
<surname>Zhang</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Gambhir</surname>
<given-names>SS</given-names>
</name>
<name>
<surname>Rao</surname>
<given-names>JH</given-names>
</name>
<name>
<surname>Wu</surname>
<given-names>JC</given-names>
</name>
</person-group>
<article-title>Quantum dot imaging for embryonic stem cells</article-title>
<source>BMC Biotechnol</source>
<year>2007</year>
<volume>7</volume>
<fpage>67</fpage>
<pub-id pub-id-type="pmid">17925032</pub-id>
<pub-id pub-id-type="doi">10.1186/1472-6750-7-67</pub-id>
</citation>
</ref>
<ref id="B31">
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Michalet</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Pinaud</surname>
<given-names>FF</given-names>
</name>
<name>
<surname>Bentolila</surname>
<given-names>LA</given-names>
</name>
<name>
<surname>Tsay</surname>
<given-names>JM</given-names>
</name>
<name>
<surname>Doose</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Li</surname>
<given-names>JJ</given-names>
</name>
<name>
<surname>Sundaresan</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Wu</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Gambhir</surname>
<given-names>SS</given-names>
</name>
<name>
<surname>Weiss</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Quantum dots for live cells, in vivo imaging, and diagnostics</article-title>
<source>Science</source>
<year>2005</year>
<volume>307</volume>
<fpage>538</fpage>
<lpage>544</lpage>
<pub-id pub-id-type="pmid">15681376</pub-id>
<pub-id pub-id-type="doi">10.1126/science.1104274</pub-id>
</citation>
</ref>
</ref-list>
</back>
</pmc>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001B06 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001B06 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Sante
   |area=    LymphedemaV1
   |flux=    Pmc
   |étape=   Corpus
   |type=    RBID
   |clé=     PMC:2375898
   |texte=   Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i   -Sk "pubmed:18430208" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd   \
       | NlmPubMed2Wicri -a LymphedemaV1 

Wicri

This area was generated with Dilib version V0.6.31.
Data generation: Sat Nov 4 17:40:35 2017. Site generation: Tue Feb 13 16:42:16 2024