Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping

Abstract

The use of near-infrared or infrared photons is a promising approach for biomedical imaging in living tissue1. This technology often requires exogenous contrast agents with combinations of hydrodynamic diameter, absorption, quantum yield and stability that are not possible with conventional organic fluorophores. Here we show that the fluorescence emission of type II2,3 quantum dots can be tuned into the near infrared while preserving absorption cross-section, and that a polydentate phosphine coating renders them soluble, disperse and stable in serum. We then demonstrate that these quantum dots allow a major cancer surgery, sentinel lymph node mapping4,5,6, to be performed in large animals under complete image guidance. Injection of only 400 pmol of near-infrared quantum dots permits sentinel lymph nodes 1 cm deep to be imaged easily in real time using excitation fluence rates of only 5 mW/cm2. Taken together, the chemical, optical and in vivo data presented in this study demonstrate the potential of near-infrared quantum dots for biomedical imaging.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Physical and optical properties of aqueous-soluble, NIR type II QDs.
Figure 2: NIR QD sentinel lymph node mapping in the mouse and pig.
Figure 3: Post-resection inspection of the surgical field and evaluation of NIR QD lymph node retention.

References

  1. 1

    Lim, Y.T. et al. Selection of quantum dot wavelengths for biomedical assays and imaging. Mol. Imaging 2, 50–64 (2003).

    CAS  Article  Google Scholar 

  2. 2

    Hatami, F. et al. Carrier dynamics in type-II GaSb/GaAs quantum dots. Phys. Rev. B 57, 4635–4641 (1998).

    CAS  Article  Google Scholar 

  3. 3

    Kim, S., Fisher, B., Eisler, H.J. & Bawendi, M. Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. J. Am. Chem. Soc. 125, 11466–11467 (2003).

    CAS  Article  Google Scholar 

  4. 4

    Jakub, J.W., Pendas, S. & Reintgen, D.S. Current status of sentinel lymph node mapping and biopsy: facts and controversies. Oncologist 8, 59–68 (2003).

    Article  Google Scholar 

  5. 5

    Bonnema, J. & Van, D.V.C.J. Sentinel lymph node biopsy in breast cancer. Ann. Oncol. 13, 1531–1537 (2002).

    CAS  Article  Google Scholar 

  6. 6

    Thompson, J.F. & Uren, R.F. Lymphatic mapping and sentinel node biopsy for melanoma. Expert. Rev. Anticancer Ther. 1, 446–452 (2001).

    CAS  Article  Google Scholar 

  7. 7

    Kim, S. & Bawendi, M.G. Oligomeric ligands for luminescent and stable nanocrystal quantum dots. J. Am. Chem. Soc. in the press (2003).

  8. 8

    Uren, R.F. & Hoefnagel, C.A. in Textbook of Melanoma (eds. J.F. Thompson, D.M. Morton & B.B.R. Kroon) Chapter 30 (Martin Dunitz, London, 2003).

    Google Scholar 

  9. 9

    Nakayama, A., Bianco, A.C., Zhang, C.Y., Lowell, B.B. & Frangioni, J.V. Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. Mol. Imaging 2, 37–49 (2003).

    Article  Google Scholar 

  10. 10

    Manna, L., Scher, E.C., Li, L.S. & Alivisatos, A.P. Epitaxial growth and photochemical annealing of graded CdS/ZnS shells on colloidal CdSe nanorods. J. Am. Chem. Soc. 124, 7136–7145 (2002).

    CAS  Article  Google Scholar 

  11. 11

    Wang, Y., Tang, Z., Correa-Duarte, M.A., Liz-Marzan, L.M. & Kotov, N.A. Multicolor luminescence patterning by photoactivation of semiconductor nanoparticle films. J. Am. Chem. Soc. 125, 2830–2831 (2003).

    CAS  Article  Google Scholar 

  12. 12

    Nakayama, A., del Monte, F., Hajjar, R.J. & Frangioni, J.V. Functional near-infrared fluorescence imaging for cardiac surgery and targeted gene therapy. Mol. Imaging 1, 365–377 (2002).

    Article  Google Scholar 

  13. 13

    Ntziachristos, V., Bremer, C. & Weissleder, R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur. Radiol. 13, 195–208 (2003).

    PubMed  Google Scholar 

  14. 14

    Sevick-Muraca, E.M., Houston, J.P. & Gurfinkel, M. Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents. Curr. Opin. Chem. Biol. 6, 642–650 (2002).

    CAS  Article  Google Scholar 

  15. 15

    US Department of Energy. Risk Assessment Information System. http://risk.lsd.ornl.gov/tox/rap_toxp.shtml.

  16. 16

    Mikulec, F.V. Semiconductor nanocrystal colloids: manganese doped cadmium selenide, (core)shell composites for biological labeling, and highly fluorescent cadmium telluride. Ph.D. Thesis, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA (1999).

  17. 17

    Drew, M.G.B., Rice, D.A. & Williams, D.M. Synthesis of Nb(O2H5C7)3Y (Y = O, S and Se): crystal structure of oxotris(tropolonato)niobium(V) monohydrate: a seven coordinate monomer containing a terminal Nb:O bond. Inorgan. Chim. Acta 118, 165–168 (1986).

    CAS  Article  Google Scholar 

  18. 18

    De Grand, A.M. & Frangioni, J.V. An operational near-infrared fluorescence imaging system prototype for large animal surgery. Technol. Cancer. Res. Treat. in the press (2003).

Download references

Acknowledgements

We thank Grisel Rivera for administrative assistance and Daniel A. Brown (BIDMC) for frozen sectioning. This work was supported by the Post-Doctoral Fellowship Program of the Korea Science and Engineering Foundation (KOSEF; Y.T.L.). This work was also supported in part by the US National Science Foundation–Materials Research Science and Engineering Center program under grant DMR-9808941 (M.G.B.), the US Office of Naval Research (M.G.B.), the Stewart Trust of Washington, D.C. (J.V.F.), US Department of Energy (Office of Biological and Environmental Research) grant DE-FG02-01ER63188 (J.V.F.) and US National Institutes of Health grant R21 EB-00673 (J.V.F. and M.G.B.).

Author information

Affiliations

Authors

Corresponding author

Correspondence to John V Frangioni.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kim, S., Lim, Y., Soltesz, E. et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22, 93–97 (2004). https://doi.org/10.1038/nbt920

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing