Molecular Imaging and Biology

, Volume 12, Issue 4, pp 394–405 | Cite as

Fluorescence Imaging and Whole-Body Biodistribution of Near-Infrared-Emitting Quantum Dots after Subcutaneous Injection for Regional Lymph Node Mapping in Mice

  • Emilie Pic
  • Thomas Pons
  • Lina Bezdetnaya
  • Agnès Leroux
  • François Guillemin
  • Benoît Dubertret
  • Frédéric MarchalEmail author
Research Article



This study compares fluorescence imaging to mass spectroscopy (inductively coupled plasma–mass spectroscopy, ICP–MS) for detection of quantum dots (QDs) in sentinel lymph node (LN) mapping of breast cancer.


We study the accumulation of near-infrared-emitting QDs into regional LNs and their whole-body biodistribution in mice after subcutaneous injection, using in vivo fluorescence imaging and ex vivo elemental analysis by ICP–MS.


We show that the QD accumulation in regional LNs is detectable by fluorescence imaging as early as 5 min post-delivery. Their concentration reaches a maximum at 4 h then decreases over a 10-day observation period. These data are confirmed by ICP–MS. The QD uptake in other organs, assessed by ICP–MS, increases steadily over time; however, its overall level remains rather low.


Fluorescence imaging can be used as a non-invasive alternative to ICP–MS to follow the QD accumulation kinetics into regional LNs.

Key words

Quantum dots Lymph nodes Near-infrared fluorescence imaging Mass spectroscopy Biodistribution 


% ID

Percentage of injected dose




Axillary lymph node


Axillary lymph node dissection


Arbitrary unit


Dynamic light scattering


Dipalmitoyl phosphotidylethanolamine


Hematoxylin and eosin


Hydrodynamic diameter


Inductively coupled plasma–atomic emission spectroscopy


Inductively coupled plasma–mass spectroscopy




Left axillary lymph node


Light-emitting diode


Left lateral thoracic lymph node


Lymph node


Lateral thoracic lymph node


Methyl ether


Micro-positron emission tomography




Phosphate buffered saline


Polyethylene glycol




Quantum dot


Right axillary lymph node


Right lateral thoracic lymph node


Region of interest




Standard deviation


Sentinel lymph node


Sentinel lymph node biopsy


Transmission electron microscopy





This work was supported by the Institut National du Cancer (INCa), the Comités départementaux (54, 57) of the Ligue Contre le Cancer, the Ligue Nationale Contre le Cancer, and the Région Lorraine.


  1. 1.
    Marchal F, Rauch P, Morel O et al (2006) Results of preoperative lymphoscintigraphy for breast cancer are predictive of identification of axillary sentinel lymph nodes. World J Surg 30:55–62Google Scholar
  2. 2.
    Rovera F, Frattini F, Marelli M et al (2008) Axillary sentinel lymph node biopsy: an overview. Int J Surg 6 Suppl:S109–112CrossRefGoogle Scholar
  3. 3.
    Ferrari A, Rovera F, Dionigi P et al (2006) Sentinel lymph node biopsy as the new standard of care in the surgical treatment for breast cancer. Expert Rev Anticancer Ther 6:1503–1515CrossRefPubMedGoogle Scholar
  4. 4.
    Noguchi M (2002) Sentinel lymph node biopsy and breast cancer. Br J Surg 89:21–34CrossRefPubMedGoogle Scholar
  5. 5.
    Wilke LG, McCall LM, Posther KE et al (2006) Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol 13:491–500CrossRefPubMedGoogle Scholar
  6. 6.
    Sato K (2007) Current technical overviews of sentinel lymph node biopsy for breast cancer. Breast Cancer 14:354–361CrossRefPubMedGoogle Scholar
  7. 7.
    Sato K, Shigenaga R, Ueda S, Shigekawa T, Krag DN (2007) Sentinel lymph node biopsy for breast cancer. J Surg Oncol 96:322–329CrossRefPubMedGoogle Scholar
  8. 8.
    Montgomery LL, Thorne AC, Van Zee KJ et al (2002) Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer. Anesth Analg 95:385–388CrossRefPubMedGoogle Scholar
  9. 9.
    Scherer K, Studer W, Figueiredo V, Bircher AJ (2006) Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes. Ann Allergy Asthma Immunol 96:497–500CrossRefPubMedGoogle Scholar
  10. 10.
    Mujtaba B, Adenaike M, Yaganti V, Mujtaba N, Jain D (2007) Anaphylactic reaction to Tc-99 m sestamibi (Cardiolite) during pharmacologic myocardial perfusion imaging. J Nucl Cardiol 14:256–258CrossRefPubMedGoogle Scholar
  11. 11.
    Chicken DW, Mansouri R, Ell PJ, Keshtgar MR (2007) Allergy to technetium-labelled nanocolloidal albumin for sentinel node identification. Ann R Coll Surg Engl 89:W12–W13CrossRefPubMedGoogle Scholar
  12. 12.
    Kaleya RN, Heckman JT, Most M, Zager JS (2005) Lymphatic mapping and sentinel node biopsy: a surgical perspective. Semin Nucl Med 35:129–134CrossRefPubMedGoogle Scholar
  13. 13.
    Murray CB, Norris DG, Bawendi MG (1993) Synthesis and characterization of nearly monodisperse CdE (E-S, Se, Te) semiconductor nanocrystallites. J Am Chem Soc 115:8706–8715CrossRefGoogle Scholar
  14. 14.
    Alivisatos AP (1996) Semiconductor clusters, nanocrystals, and quantum dots. Science 271:933–937CrossRefGoogle Scholar
  15. 15.
    Bruchez M Jr, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016CrossRefPubMedGoogle Scholar
  16. 16.
    Ipe BI, Lehnig M, Niemeyer CM (2005) On the generation of free radical species from quantum dots. Small 1:706–709CrossRefPubMedGoogle Scholar
  17. 17.
    Derfus A, Chan WCW, Bhatia S (2004) Probing the cytotoxicity of CdSe quantum dots with surface modification. Nano Lett 4:11–18CrossRefGoogle Scholar
  18. 18.
    Yu WW, Chang E, Drezek R, Colvin VL (2006) Water-soluble quantum dots for biomedical applications. Biochem Biophys Res Commun 348:781–786CrossRefPubMedGoogle Scholar
  19. 19.
    Carion O, Mahler B, Pons T, Dubertret B (2007) Synthesis, encapsulation, purification and coupling of single quantum dots in phospholipid micelles for their use in cellular and in vivo imaging. Nat Protoc 2:2383–2390CrossRefPubMedGoogle Scholar
  20. 20.
    Pons T, Lequeux N, Mahler B et al (2009) Synthesis of near-infrared-emitting, water-soluble CdTeSe/CdZnS core/shell quantum dots. Chem Mater 21(8):1418–1424CrossRefGoogle Scholar
  21. 21.
    Soltesz EG, Kim S, Kim SW et al (2006) Sentinel lymph node mapping of the gastrointestinal tract by using invisible light. Ann Surg Oncol 13:386–396CrossRefPubMedGoogle Scholar
  22. 22.
    Parungo CP, Colson YL, Kim SW et al (2005) Sentinel lymph node mapping of the pleural space. Chest 127:1799–1804CrossRefPubMedGoogle Scholar
  23. 23.
    Soltesz EG, Kim S, Laurence RG et al (2005) Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots. Ann Thorac Surg 79:269–277CrossRefPubMedGoogle Scholar
  24. 24.
    Parungo CP, Ohnishi S, Kim SW et al (2005) Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. J Thorac Cardiovasc Surg 129:844–850CrossRefPubMedGoogle Scholar
  25. 25.
    Tanaka E, Choi HS, Fujii H, Bawendi MG, Frangioni JV (2006) Image-guided oncologic surgery using invisible light: completed pre-clinical development for sentinel lymph node mapping. Ann Surg Oncol 13:1671–1681CrossRefPubMedGoogle Scholar
  26. 26.
    Kim S, Lim YT, Soltesz EG et al (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22:93–97CrossRefPubMedGoogle Scholar
  27. 27.
    Kobayashi H, Hama Y, Koyama Y et al (2007) Simultaneous Multicolor Imaging of Five Different Lymphatic Basins Using Quantum Dots. Nano Lett 7:1711–1716CrossRefPubMedGoogle Scholar
  28. 28.
    Hama Y, Koyama Y, Urano Y, Choyke PL, Kobayashi H (2007) Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity. Breast Cancer Res Treat 103:23–28CrossRefPubMedGoogle Scholar
  29. 29.
    Ballou B, Ernst LA, Andreko S et al (2007) Sentinel lymph node imaging using quantum dots in mouse tumor models. Bioconjug Chem 18:389–396CrossRefPubMedGoogle Scholar
  30. 30.
    Knapp DW, Adams LG, Degrand AM et al (2007) Sentinel lymph node mapping of invasive urinary bladder cancer in animal models using invisible light. Eur Urol 52:1700–1708CrossRefPubMedGoogle Scholar
  31. 31.
    Chen Z, Chen H, Meng H et al (2008) Bio-distribution and metabolic paths of silica coated CdSeS quantum dots. Toxicol Appl Pharmacol 230:364–371CrossRefPubMedGoogle Scholar
  32. 32.
    Fischer H, Liu L, Pang K, Chan W (2006) Pharmacokinetics of nanoscale quantum dots: in vivo distribution, sequestration, and clearance in the rat. Adv Funct Mater 16:1299–1305CrossRefGoogle Scholar
  33. 33.
    Gopee NV, Roberts DW, Webb P et al (2007) Migration of intradermally injected quantum dots to sentinel organs in mice. Toxicol Sci 98:249–257CrossRefPubMedGoogle Scholar
  34. 34.
    Yang RS, Chang LW, Wu JP et al (2007) Persistent tissue kinetics and redistribution of nanoparticles, quantum dot 705, in Mice: ICP–MS quantitative assessment. Environ Health Perspect 115:1339–1343CrossRefPubMedGoogle Scholar
  35. 35.
    Duconge F, Pons T, Pestourie C et al (2008) Fluorine-18-Labeled phospholipid quantum dot micelles for in vivo multimodal imaging from whole body to cellular scales. Bioconjug Chem 19:1921–1926CrossRefPubMedGoogle Scholar
  36. 36.
    Lin P, Chen JW, Chang LW et al (2008) Computational and ultrastructural toxicology of a nanoparticle, quantum dot 705, in mice. Environ Sci Technol 42:6264–6270CrossRefPubMedGoogle Scholar
  37. 37.
    Geys J, Nemmar A, Verbeken E et al (2008) Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge. Environ Health Perspect 116:1607–1613CrossRefPubMedGoogle Scholar
  38. 38.
    Daou TJ, Li L, Reiss P, Josserand V, Texier I (2009) Effect of poly(ethylene glycol) length on the in vivo behavior of coated quantum dots. Langmuir 25(5):3040–3044CrossRefPubMedGoogle Scholar
  39. 39.
    Kostarelos K (2009) Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration. Mol Pharma 6(2):520–530CrossRefGoogle Scholar
  40. 40.
    Pic E, Bezdetnaya L, Guillemin F, Marchal F (2009) Quantification techniques and biodistribution of semiconductor quantum dots. Anticancer Agents Med Chem 9:295–303PubMedGoogle Scholar
  41. 41.
    Dubertret B, Skourides P, Norris DJ et al (2002) In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298:1759–1762CrossRefPubMedGoogle Scholar
  42. 42.
    Hama Y, Koyama Y, Urano Y, Choyke PL, Kobayashi H (2007) Two-color lymphatic mapping using Ig-conjugated near infrared optical probes. J Invest Dermatol 127:2351–2356CrossRefPubMedGoogle Scholar
  43. 43.
    Robe A, Pic E, Lassalle HP et al (2008) Quantum dots in axillary lymph node mapping: biodistribution study in healthy mice. BMC Cancer 8:111CrossRefPubMedGoogle Scholar
  44. 44.
    Ntziachristos V, Bremer C, Weissleder R (2003) Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 13:195–208PubMedGoogle Scholar
  45. 45.
    Ntziachristos V, Ripoll J, Wang LV, Weissleder R (2005) Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol 23:313–320CrossRefPubMedGoogle Scholar
  46. 46.
    Tanis PJ, Nieweg OE, Valdes Olmos RA, Kroon BB (2001) Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy. J Am Coll Surg 192:399–409CrossRefPubMedGoogle Scholar
  47. 47.
    Maysinger D, Behrendt M, Lalancette-Hebert M, Kriz J (2007) Real-time imaging of astrocyte response to quantum dots: in vivo screening model system for biocompatibility of nanoparticles. Nano Lett 7:2513–2520CrossRefPubMedGoogle Scholar
  48. 48.
    Clift MJ, Rothen-Rutishauser B, Brown DM et al (2008) The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line. Toxicol Appl Pharmacol 232:418–427CrossRefPubMedGoogle Scholar
  49. 49.
    Wang L, Nagesha DK, Selvarasah S, Dokmeci MR, Carrier RL (2008) Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures. J Nanobiotechnol 6:11CrossRefGoogle Scholar
  50. 50.
    Stern ST, Zolnik BS, McLeland CB et al (2008) Induction of autophagy in porcine kidney cells by quantum dots: a common cellular response to nanomaterials? Toxicol Sci 106:140–152CrossRefPubMedGoogle Scholar
  51. 51.
    Jacobsen NR, Moller P, Jensen KA et al (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE−/− mice. Part Fibre Toxicol 6:2CrossRefPubMedGoogle Scholar
  52. 52.
    Diagaradjane P, Orenstein-Cardona JM, Colon-Casasnovas EN et al (2008) Imaging epidermal growth factor receptor expression in vivo: pharmacokinetic and biodistribution characterization of a bioconjugated quantum dot nanoprobe. Clin Cancer Res 14:731–741CrossRefPubMedGoogle Scholar
  53. 53.
    Soo Choi H, Liu W, Misra P et al (2007) Renal clearance of quantum dots. Nat Biotechnol 25:1165–1170CrossRefGoogle Scholar
  54. 54.
    Schipper ML, Cheng Z, Lee SW et al (2007) microPET-based biodistribution of quantum dots in living mice. J Nucl Med 48:1511–1518CrossRefPubMedGoogle Scholar
  55. 55.
    Schipper ML, Iyer G, Koh AL et al (2009) Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. Small 5:126–134CrossRefPubMedGoogle Scholar
  56. 56.
    Gao X, Chen J, Chen J et al (2008) Quantum dots bearing lectin-functionalized nanoparticles as a platform for in vivo brain imaging. Bioconjug Chem 19:2189–2195CrossRefPubMedGoogle Scholar
  57. 57.
    Chen K, Li ZB, Wang H, Cai W, Chen X (2008) Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots. Eur J Nucl Med Mol Imaging 35:2235–2244CrossRefPubMedGoogle Scholar

Copyright information

© Academy of Molecular Imaging 2009

Authors and Affiliations

  • Emilie Pic
    • 1
  • Thomas Pons
    • 2
  • Lina Bezdetnaya
    • 1
  • Agnès Leroux
    • 3
  • François Guillemin
    • 1
  • Benoît Dubertret
    • 2
  • Frédéric Marchal
    • 1
    Email author
  1. 1.Centre de Recherche en Automatique de Nancy—Nancy-University—CNRS—Centre Alexis VautrinVandoeuvre-lès-Nancy CedexFrance
  2. 2.Laboratoire Photons et MatièreCNRS UPRA0005, ESPCIParisFrance
  3. 3.Department of PathologyCentre Alexis VautrinVandoeuvre-lès-Nancy CedexFrance

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