Abstract
The use of short-wave infrared (SWIR) light for fluorescence bioimaging offers the advantage of reduced photon scattering and improved tissue penetration compared to traditional shorter wavelength imaging approaches. While several nanomaterials have been shown capable of generating SWIR emissions, rare-earth-doped nanoparticles (REs) have emerged as an exceptionally bright and biocompatible class of SWIR emitters. Here, we demonstrate SWIR imaging of REs for several applications, including lymphatic mapping, real-time monitoring of probe biodistribution, and molecular targeting of the αvβ3 integrin in a tumor model. We further quantified the resolution and depth penetration limits of SWIR light emitted by REs in a customized imaging unit engineered for SWIR imaging of live small animals. Our results indicate that SWIR light has broad utility for preclinical biomedical imaging and demonstrates the potential for molecular imaging using targeted REs.
Highlights
Imaging approaches that are able to resolve the physiological and molecular complexity of cancer can provide deep insight into the underlying causes of disease development, improve our understanding of treatment responses, and lead to better patient prognoses.[1,2,3] Molecular imaging approaches, in particular, offer a means by which to monitor the dynamics of cancer progression, permitting their use in a wide variety of clinical applications ranging from assessment of tumor metabolism to in situ molecular profiling.[4,5,6] current imaging efforts are limited by the availability of contrast agents with the requisite properties for enabling rapid resolution of molecular features within biological tissue
Rare-earth-doped nanoparticles were first synthesized according to a well-established thermal decomposition method and were composed of an ytterbium (Yb)- and erbium (Er)-doped NaYF4 core surrounded by an undoped NaYF4 shell.[36]
Optical imaging has relied on the use of shorter wavelengths of light (
Summary
Imaging approaches that are able to resolve the physiological and molecular complexity of cancer can provide deep insight into the underlying causes of disease development, improve our understanding of treatment responses, and lead to better patient prognoses.[1,2,3] Molecular imaging approaches, in particular, offer a means by which to monitor the dynamics of cancer progression, permitting their use in a wide variety of clinical applications ranging from assessment of tumor metabolism to in situ molecular profiling.[4,5,6] current imaging efforts are limited by the availability of contrast agents with the requisite properties for enabling rapid resolution of molecular features within biological tissue. In contrast to other molecular imaging modalities, optical imaging offers remarkable detection sensitivity and the ability to conduct real-time image acquisition.[7,8,9] Traditionally, optical imaging has relied on the use of visible or near-infrared (NIR) light. Photons in these spectral regions are heavily scattered as they pass through biological tissue and produce background autofluorescence generated by tissue components. These limitations result in limited photon penetration, poor image resolution, and a low signal to noise ratio for distinguishing targets of interest.[10,11,12] In contrast, recent reports describing imaging with NIR-II or short-wave infrared (SWIR) light have shown this spectral region (1000-2300 nm) exhibiting reduced light scattering, improved photon penetrance, and exceptionally low autofluorescence.[13,14,15]
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