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

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.

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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.

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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.).

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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

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Correspondence to John V Frangioni.

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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

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