27 February 2009 Development of a targeted CT contrast agent: assessment of cellular interactions using novel integrated optical labels
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Computed tomography (CT) enables high resolution, whole-body imaging with excellent depth penetration. The development of new targeted radiopaque CT contrast agents can provide the required sensitivity and localization for the successful detection and diagnosis of smaller lesions representing earlier disease. Nanoscale, perfluorooctylbromide (C8F17Br, PFOB) droplets have previously been used as untargeted contrast agents in X-ray imaging, and form the basis of a promising new group of agents that can be developed for targeted CT imaging. For successful targeting to disease sites, new PFOB droplet formulations tailored for ideal in vivo performance (e.g., biodistribution, toxicity, and pharmacokinetics) must be developed. However, the direct assessment of PFOB agents in biological environments early in their development is difficult using CT, as its sensitivity is not adequate for identification of single probes in vitro or in vivo. In order to allow single droplet interactions with cells to be directly assessed using standard cellular imaging tools, we integrate an optical marker within the PFOB agent. In this work, a new method to label a PFOB agent with fluorescent quantum dot (QD) nanoparticles is presented. These composite PFOB-QD droplets loaded into macrophage cells result in fluorescence on a cellular level that correlates well to the strong CT contrast exhibited in corresponding tissue-mimicking cell pellets. QD loading within the PFOB droplet core allows optical labeling without influencing the surface-dependent properties of the PFOB droplets in vivo, and may be used to follow PFOB localization from in vitro cell studies to histopathology.
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Naomi Matsuura, Naomi Matsuura, Melissa L. Hill, Melissa L. Hill, Ivan Gorelikov, Ivan Gorelikov, Siqi Zhu, Siqi Zhu, Kelvin Wan, Kelvin Wan, James G. Mainprize, James G. Mainprize, Martin J. Yaffe, Martin J. Yaffe, J. A. Rowlands, J. A. Rowlands, "Development of a targeted CT contrast agent: assessment of cellular interactions using novel integrated optical labels", Proc. SPIE 7262, Medical Imaging 2009: Biomedical Applications in Molecular, Structural, and Functional Imaging, 72622A (27 February 2009); doi: 10.1117/12.812048; https://doi.org/10.1117/12.812048

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