Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping (original) (raw)

Nature Biotechnology volume 22, pages 93–97 (2004)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Lim, Y.T. et al. Selection of quantum dot wavelengths for biomedical assays and imaging. Mol. Imaging 2, 50–64 (2003).
    Article CAS Google Scholar
  2. Hatami, F. et al. Carrier dynamics in type-II GaSb/GaAs quantum dots. Phys. Rev. B 57, 4635–4641 (1998).
    Article CAS Google Scholar
  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).
    Article CAS Google Scholar
  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. Bonnema, J. & Van, D.V.C.J. Sentinel lymph node biopsy in breast cancer. Ann. Oncol. 13, 1531–1537 (2002).
    Article CAS Google Scholar
  6. Thompson, J.F. & Uren, R.F. Lymphatic mapping and sentinel node biopsy for melanoma. Expert. Rev. Anticancer Ther. 1, 446–452 (2001).
    Article CAS Google Scholar
  7. Kim, S. & Bawendi, M.G. Oligomeric ligands for luminescent and stable nanocrystal quantum dots. J. Am. Chem. Soc. in the press (2003).
  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. 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. 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).
    Article CAS Google Scholar
  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).
    Article CAS Google Scholar
  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. 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. 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).
    Article CAS Google Scholar
  15. US Department of Energy. Risk Assessment Information System. http://risk.lsd.ornl.gov/tox/rap_toxp.shtml.
  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. 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).
    Article CAS Google Scholar
  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

Author notes

  1. Yong Taik Lim
    Present address: Electronics and Telecommunications Research Institute, 161 Gajeong-dong, Yuseong-gu, Daejeon, 305-350, Republic of Korea
  2. Sungjee Kim and Yong Taik Lim: These authors contributed equally to this study.

Authors and Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA
    Sungjee Kim & Moungi G Bawendi
  2. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, 02215, Massachusetts, USA
    Yong Taik Lim, Alec M De Grand, Jaihyoung Lee, Akira Nakayama & John V Frangioni
  3. Division of Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, 02115, Massachusetts, USA
    Edward G Soltesz, Tomislav Mihaljevic, Rita G Laurence, Delphine M Dor & Lawrence H Cohn
  4. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, 02215, Massachusetts, USA
    J Anthony Parker & John V Frangioni

Authors

  1. Sungjee Kim
    You can also search for this author inPubMed Google Scholar
  2. Yong Taik Lim
    You can also search for this author inPubMed Google Scholar
  3. Edward G Soltesz
    You can also search for this author inPubMed Google Scholar
  4. Alec M De Grand
    You can also search for this author inPubMed Google Scholar
  5. Jaihyoung Lee
    You can also search for this author inPubMed Google Scholar
  6. Akira Nakayama
    You can also search for this author inPubMed Google Scholar
  7. J Anthony Parker
    You can also search for this author inPubMed Google Scholar
  8. Tomislav Mihaljevic
    You can also search for this author inPubMed Google Scholar
  9. Rita G Laurence
    You can also search for this author inPubMed Google Scholar
  10. Delphine M Dor
    You can also search for this author inPubMed Google Scholar
  11. Lawrence H Cohn
    You can also search for this author inPubMed Google Scholar
  12. Moungi G Bawendi
    You can also search for this author inPubMed Google Scholar
  13. John V Frangioni
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toJohn V Frangioni.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights 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

Associated content