Near-Infrared Fluorescent Quantam Dots for Lymph Node

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

Sungjee Kim1, 6, Yong Taik Lim2, 5, 6, Edward G Soltesz3, Alec M De Grand2, Jaihyoung Lee2, Akira Nakayama2, J Anthony Parker4, Tomislav Mihaljevic3, Rita G Laurence3, Delphine M Dor3, Lawrence H Cohn3, Moungi G Bawendi1 & John V Frangioni2, 4

1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. 2. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 3. Division of Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. 4. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 5. Present address: Electronics and Telecommunications Research Institute, 161 Gajeong-dong, Yuseong-gu, Daejeon, 305-350, Republic of Korea. 6. These authors contributed equally to this study. Correspondence should be addressed to J V Frangioni. e-mail: jfrangio@bidmc.harvard.edu

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 mapping4-6, 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.

Nature Biotechnology, Published online: 7 December 2003, doi:10.1038/nbt920 January 2004 Volume 22 Number 1 pp 93 - 97

In LAY Terms:

Cancer biopsies on the dot

Scientists have developed an improved method for performing sentinel lymph node biopsy, a crucial first step in determining whether a cancer has spread to other parts of the body. The new method, reported in the January 2004 issue of Nature Biotechnology, relies on tiny fluorescent crystals known as "quantum dots" to detect sentinel lymph nodes.

The body's lymphatic system drains fluid and cells to lymph nodes that contain cancer-fighting white blood cells. If cells have migrated from the initial tumor to the lymph node, it is a warning that cancer is spreading in the body. A sentinel lymph node is the first lymph node to receive drainage from a cancer-containing tissue. Compared with traditional surgeries, sentinel lymph node biopsy reduces surgical trauma for the patient and gives more reliable results by limiting the biopsy to a single lymph node. An important breakthrough in surgical oncology, it is being applied to an increasing number of solid tumors.

Using current biopsy methods, however, it is difficult for surgeons to detect sentinel lymph nodes, and first incisions have to be made essentially blindly by very experienced surgeons. John V. Frangioni, Moungi G. Bawendi and colleagues have shown that, by labeling sentinel lymph nodes with quantum dots, surgeons can see the nodes through at least one centimeter of tissue and accurately guide the surgery. The new method is also useful for ensuring that resection of the sentinel lymph node is complete.

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