Abstract
Cerenkov luminescence imaging (CLI) has been successfully utilized in various fields of preclinical studies; however, CLI is challenging due to its weak luminescent intensity and insufficient penetration capability. Here, we report the design and synthesis of a type of rare-earth microparticles (REMPs), which can be dually excited by Cerenkov luminescence (CL) resulting from the decay of radionuclides to enhance CLI in terms of intensity and penetration. Methods: Yb3+- and Er3+- codoped hexagonal NaYF4 hollow microtubes were synthesized via a hydrothermal route. The phase, morphology, and emission spectrum were confirmed for these REMPs by power X-ray diffraction (XRD), scanning electron microscopy (SEM), and spectrophotometry, respectively. A commercial CCD camera equipped with a series of optical filters was employed to quantify the intensity and spectrum of CLI from radionuclides. The enhancement of penetration was investigated by imaging studies of nylon phantoms and nude mouse pseudotumor models. Results: the REMPs could be dually excited by CL at the wavelengths of 520 and 980 nm, and the emission peaks overlaid at 660 nm. This strategy approximately doubled the overall detectable intensity of CLI and extended its maximum penetration in nylon phantoms from 5 to 15 mm. The penetration study in living animals yielded similar results. Conclusions: this study demonstrated that CL can dually excite REMPs and that the overlaid emissions in the range of 660 nm could significantly enhance the penetration and intensity of CL. The proposed enhanced CLI strategy may have promising applications in the future.
Highlights
Nuclear imaging allows for sensitive and noninvasive measurement of radionuclide-labeled probes in living animals and humans [1]
Optical imaging is of much lower expense and higher throughput, it is still limited by the paucity of available imaging agents for clinical use, with only three non-specific agents approved by the US Food and Drug Administration (FDA): indocyanine green (ICG), methylene blue, and fluorescein [3]
Synthesis and characterization of rare-earth microparticles (REMPs) NaYF4 microparticles codoped with Yb3+ and Er3+ ions were synthesized by a hydrothermal method
Summary
Nuclear imaging allows for sensitive and noninvasive measurement of radionuclide-labeled probes in living animals and humans [1]. Optical imaging is of much lower expense and higher throughput, it is still limited by the paucity of available imaging agents for clinical use, with only three non-specific agents approved by the US Food and Drug Administration (FDA): indocyanine green (ICG), methylene blue, and fluorescein [3]. Because many radionuclides (e.g. 131I, 18F) approved by the FDA for clinical use are emit charged particles, capable of producing CL that can be detected by low-cost chargecoupled device (CCD) cameras [4,5]. The concept of Cerenkov luminescence imaging (CLI) provides a potential method to achieve multimodality molecular imaging by combining radionuclide labeled probes and optical imaging together [6]. Since 2009, CLI has been successfully utilized in various fields of preclinical study, including in vivo tumor imaging [5,7,8], therapy monitoring [9], intra-operative guidance [10], lymphography [11], endoscopy [3,12] and in vivo 3-dimensional reconstruction [13,14,15]
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