title: Quantum dots in axillary lymph node mapping: biodistribution study in healthy mice.
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 microL of 1 microM (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CRAN, Nancy-University, CNRS, Centre Alexis Vautrin, Avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France. a.robe@nancy.fnclcc.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Robe
authors.forename: Emilie
authors.initials: E
authors.lastname: Pic
authors.forename: Henri-Pierre
authors.initials: HP
authors.lastname: Lassalle
authors.forename: Lina
authors.initials: L
authors.lastname: Bezdetnaya
authors.forename: François
authors.initials: F
authors.lastname: Guillemin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Marchal
mesh_terms: D000818:Animals; D001365:Axilla; D003287:Contrast Media / Q000493:pharmacokinetics*; D003581:Cytodiagnosis / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D008198:Lymph Nodes / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D045663:Quantum Dots; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes