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 tissue. 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 II 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 mapping, 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/cm(2). Taken together, the chemical, optical and in vivo data presented in this study demonstrate the potential of near-infrared quantum dots for biomedical imaging.

In vivo quantum dot labeling of mammalian stem and progenitor cells

“…QDs may possess significant advantages over current methods to label transplanted cells, which have been hampered by both safety issues (e.g., the use of engineered viruses as vectors) and the ability of cells to reliably and permanently express a given factor (e.g., the use of liposomes or naked DNA). Experiments outside of the nervous system have demonstrated that QDs may be superior in certain human diagnostic clinical applications such as the identification of tumor-positive sentinel lymph nodes (Kim et al, 2004;Soltesz et al, 2005Soltesz et al, , 2006. Our in vivo demonstration of the lack of toxicity using the developing embryo and nervous system support the further exploration of QDs as diagnostic and therapeutic tools for human disease.…”

“…This novel demonstration reveals that QD loading does not interfere with the ability of NSPCs to differentiate into the mature neuronal and glial lineages of the mammalian nervous system. The majority of in vitro studies to date have not found any adverse effects of QDs on cell viability, morphology, or function (Ballou et al, 2004;Kim et al, 2004) provided the QDs were capped by both ZnS and hydrophilic shells. However, it has been shown that surface modifications can modulate the biocompatibility of QDs used in certain applications (Shiohara et al, 2004;Kirchner et al, 2005).…”

Silica-Coated CdTe Quantum Dots Functionalized with Thiols for Bioconjugation to IgG Proteins

“…9 For instance, the ability to conduct bioimaging over extended periods of time without decomposition was demonstrated with phosphine-coated QDs for in vivo site-directed surgeries. 10 The control over surface properties of QDs is especially crucial to maintain desirable fluorescent properties and aqueous solubility. Functionalization of the nanoparticle surface is also important to prepare the surface to be exploited for bioconjugation purposes.…”

An Enzymatically Activated Fluorescence Probe for Targeted Tumor Imaging

“…For example, in the clinical field, video-assisted laparoscopic surgery is becoming one of the standard methods for resecting metastases, 27 and it already relies on optical cameras that could easily be adapted to employ fluorescence imaging. 28 Probes such as TG-βGal have appropriate characteristics (high molar extinction coefficient and high fluorescence quantum yield in aqueous media after reaction with the target enzymes) for visualization of surface tumors such as intraperitoneal tumors, for which brightness of the fluorophores is more important than long-wavelength excitability, as the light does not need to penetrate the skin and tissues. Our aim in the present work was to design a TG-βGal-based probe that would be suitable for in vivo tumor imaging and to test its suitability for this purpose in an animal tumor model.…”