Sentinel Lymph Node Mapping With Type-II Quantum Dots

Division of Hematology/Oncology, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Methods in Molecular Biology (Impact Factor: 1.29). 02/2007; 374:147-59. DOI: 10.1385/1-59745-369-2:147
Source: PubMed


Sentinel lymph node (SLN) mapping is an important cancer surgery during which the first lymph node draining the site of a tumor is identified, resected, and analyzed for the presence or absence of malignant cells. Fluorescent semiconductor nanocrystals (quantum dots [QDs]) of the appropriate size, charge, and emission wavelength permit this surgery to be performed rapidly, with high sensitivity and under complete image guidance. We describe the materials and methods necessary for the production and characterization of type-II near-infrared fluorescent QDs, which have been optimized for SLN mapping. They contain a CdTe core, CdSe shell, and a highly anionic, oligomeric phosphine organic coating. We also describe how to utilize such QDs in animal model systems of SLN mapping.

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Available from: Shunsuke Ohnishi
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    • "The unique optical properties and the ease of modification of QDs by some bioactive materials make these nanoparticles as highly promising fluorescent labels for in vivo biological applications [4,5]. Currently, fluorescent probes have been developed by conjugating QDs with target molecules (e.g., antibodies and peptides) and have been used for in vivo visualization of cancer cells [6], sentinel lymph node detection [7,8], and imaging of drug targeting studies [9]. More important, new synthetic techniques of QDs biologically functionalized QDs with excellent biological compatibility and water solubility, which pave the way for the application of tissue imaging in vivo[10]. "
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    ABSTRACT: The purpose of this experiment was to investigate the visible imaging of gastric adenocarcinoma cells in vitro by targeting tumor-associated glycoprotein 72 (TAG-72) with near-infrared quantum dots (QDs). QDs with an emission wavelength of about 550 to 780 nm were conjugated to CC49 monoclonal antibodies against TAG-72, resulting in a probe named as CC49-QDs. A gastric adenocarcinoma cell line (MGC80-3) expressing high levels of TAG-72 was cultured for fluorescence imaging, and a gastric epithelial cell line (GES-1) was used for the negative control group. Transmission electron microscopy indicated that the average diameter of CC49-QDs was 0.2 nm higher compared with that of the primary QDs. Also, fluorescence spectrum analysis indicated that the CC49-QDs did not have different optical properties compared to the primary QDs. Immunohistochemical examination and in vitro fluorescence imaging of the tumors showed that the CC49-QDs probe could bind TAG-72 expressed on MGC80-3 cells.
    Full-text · Article · Jun 2013 · Nanoscale Research Letters
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    • "Incubation of 99mTc-nanocolloid and ICG provided a favorable agent retention time, with the fluorescence lasting up to 19 h post-injection, for the detection of sentinel lymph nodes in the necks of patients with squamous cell carcinoma of the oral cavity [32]. In addition, another new NIR imaging approach to visualize sentinel lymph nodes has been demonstrated in animal studies using nano-carriers, such as quantum dots [31,33-35] and dendrimers [36-38]. "
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    ABSTRACT: Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy.
    Full-text · Article · Apr 2013 · EJNMMI Research
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    • "Such methods can be based on the measurement of backscattered light, on the detection of fluorescence photons [5–11] or measurement of the acoustic waves generated by the photoacoustic effect [12,13], or a combination of these [9,14]. Several tracers can be used, such as dyes, fluorescent molecules, quantum dots [15,16] or nano-objects for multimodal imaging [17–19]. They should have one absorption band in the red or near infrared range where light has its maximum depth of penetration in tissues. "
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    ABSTRACT: Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10(-4) to 1.7 × 10(-2), which was enough to allow fluorescence detection and imaging of its distribution. A detection threshold, evaluated in scattering test objects, lower than 2.5 nmol × L(-1) was obtained, using a single-probe setup with a 5-mW incident light power. The detection sensitivity using a fluorescence imaging device was in the µmol × L(-1) range, with a noncooled CCD camera. Preclinical evaluation was performed on a rat model and permitted to observe inflamed nodes on all animals.
    Full-text · Article · Sep 2012 · Biomedical Optics Express
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