Real-time optical imaging using quantum dot and related nanocrystals

Abstract

Biomedical optical imaging is rapidly evolving because of its desirable features of rapid frame rates, high sensitivity, low cost, portability and lack of radiation. Quantum dots are attractive as imaging agents owing to their high brightness, and photo- and bio-stability. Here, the current status of in vitro and in vivo real-time optical imaging with quantum dots is reviewed. In addition, we consider related nanocrystals based on solid-state semiconductors, including upconverting nanoparticles and bioluminescence resonance energy transfer quantum dots. These particles can improve the signal-to-background ratio for real-time imaging largely by suppressing background signal. Although toxicity and biodistribution of quantum dots and their close relatives remain prime concerns for translation to human imaging, these agents have many desirable features that should be explored for medical purposes.

Figure 1. Wide range of fluorescence can be emitted from quantum dots by a single excitation light with narrow emission peaks

(A) White light and spectrally unmixed fluorescence images of quantum dots (QD525, 545, 565, 585, 605, 655, 700 and 800; Invitrogen Corporation, Carlsbad, CA, USA) excited by a single blue light. (B) Spectra of emission fluorescence corresponding to each quantum dot.

Figure 2. In vivo cancer cell tracking within the lymphatic system

(A) B16 CXCR4 melanoma cells labeled with QD655. (B) Cancer cell migration to neck lymph nodes can be tracked by bright QD fluorescence with in vivo optical imaging. (C) Even after tissue processing, QD-labeled cancer cells (green) can be tracked by its bright and stable fluorescence of QDs. DIC: Differential interference contrast; QD: Quantum dot.

Figure 3. Real-time, multicolor quantum dots in vivo lymphatic imaging

(A) Real colors of QDs’ fluorescence excited by UV. Fluorescence of visible-range QDs can be identified and distinguished by their distinct colors. (B) Schematic illustration of injection sites of a mouse. (C) Five different lymphatic basins are depicted by the distinct colors corresponding to the injected QDs in real time (also see Supplementary Video 1). Lat.: Lateral; LN: Lymph node; QD: Quantum dot.

Figure 4. Real-time in vivo cancer imaging with quantum dots

Small disseminated cancer foci are endoscopically detected by quantum dot fluorescence (arrow head). Also see Supplementary Video 2.

Figure 5. In vivo lymphatic images with the bioluminescence resonance energy transfer quantum-dot nanoparticle

(A) Schematic illustration of a BRET-QD nanoparticle (reproduced with permission from Nature Publishing Group, see [75]). (B) Sentinel lymph node (left axillary) can be detected with no background signal (autofluorescence). BRET: Bioluminescence resonance energy transfer; LN: Lymph node; Lt: Left; QD: Quantum dot; Rt: Right.