Near-Infrared Gold Nanocages as a New Class of Tracers for Photoacoustic Sentinel Lymph Node Mapping on a Rat Model

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri 63130-4899, USA.
Nano Letters (Impact Factor: 13.59). 01/2009; 9(1):183-8. DOI: 10.1021/nl802746w
Source: PubMed


This work demonstrated the use of Au nanocages as a new class of lymph node tracers for noninvasive photoacoustic (PA) imaging of a sentinel lymph node (SLN). Current SLN mapping methods based on blue dye and/or nanometer-sized radioactive colloid injection are intraoperative due to the need for visual detection of the blue dye and low spatial resolution of Geiger counters in detecting radioactive colloids. Compared to the current methods, PA mapping based on Au nanocages shows a number of attractive features: noninvasiveness, strong optical absorption in the near-infrared region (for deep penetration), and the accumulation of Au nanocages with a higher concentration than the initial solution for the injection. In an animal model, these features allowed us to identify SLNs containing Au nanocages as deep as 33 mm below the skin surface with good contrast. Most importantly, compared to methylene blue Au nanocages can be easily bioconjugated with antibodies for targeting specific receptors, potentially eliminating the need for invasive axillary staging procedures in addition to providing noninvasive SLN mapping.

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    • "By combining luminescence and PA imaging modalities, a single, versatile minimally-invasive imaging platform can be designed to enable visualization for deep tissue diagnostics and potential real-time surgical guidance. Whilst there have been a few recent reports using gold nanoparticles and quantum dots for PA imaging, the clinical translation of these materials has been limited due to various issues, including the lack of absorption tunability and cytotoxicity212223. Therefore, it is very important to establish new contrast agents that: (1) have optical properties that can be easily tuned, (2) have low cytotoxicity, and (3) are able to enhance the signals for both luminescence and PA imaging24. "
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    ABSTRACT: Multi-modal imaging is an emerging area that integrates multiple imaging modalities to simultaneously capture visual information over many spatial scales. Complementary contrast agents need to be co-developed in order to achieve high resolution and contrast. In this work, we demonstrated that rare-earth doped particles (REDPs) can be employed as dual-modal imaging agents for both luminescence and photoacoustic (PA) imaging to achieve intrinsic high contrast, temporal and spatial resolution, reaching deeper depth. REDPs synthesized with different surfactants (citric acid, polyacrylic acid, ethylenediaminetetraacetic acid and sodium citrate) exhibit tunable emission properties and PA signal amplitudes. Amongst these samples, sodium citrate-modified REDPs showed the strongest PA signals. Furthermore, since REDPs have multiple absorption peaks, they offer a unique opportunity for multi-wavelength PA imaging (e.g. PA signals were measured using 520 and 975 nm excitations). The in vivo PA images around the cortical superior sagittal sinus (SSS) blood vessel captured with enhanced signal arising from REDPs demonstrated that in addition to be excellent luminescent probes, REDPs can also be used as successful PA contrast agents. Anisotropic polyacrylic acid-modified REDPs were found to be the best candidates for dual-modal luminescence and PA imaging due to their strong luminescence and PA signal intensities.
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    • "This, in turn, can give rise to heat conversion – and to the subsequent pressure wave generating the photoacoustic signal – with an especially high efficiency, due to the large absorption cross section of metal nanoparticles and to their negligible radiative relaxation. These optothermal properties have been the basis for the development of metal nanoparticles as contrast agents for photoacoustic imaging [9–19] and photoacoustic tomography [20–24]. "
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    • "Gold nanorods in particular have been targeted as potential contrast agents for PAI due to their strong tunable NIR absorption and enhancement of their photothermal properties which arise from the plasmon resonance effect [34] [35]. For example, near-infrared (NIR) absorbing gold nanocages have been successfully studied as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model [36]. Furthermore, single-walled carbon nanotubes have also shown promise as molecular contrast agents for the photoacoustic imaging of tumors when functionalized with cyclic Arg-Gly-Asp (RGD) peptides and PEGylated dendrons[9] [37] [38]. "
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