20 February 2018 Dual-radiolabeled nanoparticle probes for depth-independent in vivo imaging of enzyme activation
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Quantitative and noninvasive measurement of protease activities has remained an imaging challenge in deep tissues such as the lungs. Here, we designed a dual-radiolabeled probe for reporting the activities of proteases such as matrix metalloproteinases (MMPs) with multispectral single photon emission computed tomography (SPECT) imaging. A gold nanoparticle (NP) was radiolabeled with 125I and 111In and functionalized with an MMP9-cleavable peptide to form a multispectral SPECT imaging contrast agent. In another design, incorporation of 199Au radionuclide into the metal crystal structure of gold NPs provided a superior and stable reference signal in lungs, and 111In was linked to the NP surface via a protease-cleavable substrate, which can serve as an enzyme activity reporter. This work reveals strategies to correlate protease activities with diverse pathologies in a tissue-depth independent manner.
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Kvar C. L. Black, Kvar C. L. Black, Mingzhou Zhou, Mingzhou Zhou, Pinaki Sarder, Pinaki Sarder, Maryna Kuchuk, Maryna Kuchuk, Amal Y. Al-Yasiri, Amal Y. Al-Yasiri, Sean P. Gunsten, Sean P. Gunsten, Kexian Liang, Kexian Liang, Heather M. Hennkens, Heather M. Hennkens, Walter J. Akers, Walter J. Akers, Richard Laforest, Richard Laforest, Steven L. Brody, Steven L. Brody, Cathy S. Cutler, Cathy S. Cutler, Samuel Achilefu, Samuel Achilefu, } "Dual-radiolabeled nanoparticle probes for depth-independent in vivo imaging of enzyme activation", Proc. SPIE 10508, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications X, 1050805 (20 February 2018); doi: 10.1117/12.2301033; https://doi.org/10.1117/12.2301033

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