Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors
Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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American Chemical Society (ACS)
2018
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| Online Access: | http://hdl.handle.net/1721.1/113328 https://orcid.org/0000-0002-6945-4057 https://orcid.org/0000-0002-8163-7059 https://orcid.org/0000-0002-2834-6359 https://orcid.org/0000-0001-9157-6491 |
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| author | Paletta, Joseph T. Zhang, Hui Boska, Michael D. Ottaviani, M. Francesca Rajca, Andrzej Nguyen, Hung VanThanh Chen, Qixian Harvey, Peter Jiang, Yivan Jasanoff, Alan Pradip Johnson, Jeremiah A. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Paletta, Joseph T. Zhang, Hui Boska, Michael D. Ottaviani, M. Francesca Rajca, Andrzej Nguyen, Hung VanThanh Chen, Qixian Harvey, Peter Jiang, Yivan Jasanoff, Alan Pradip Johnson, Jeremiah A. |
| author_sort | Paletta, Joseph T. |
| collection | MIT |
| description | Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field ¹H MRI techniques. |
| first_indexed | 2024-09-23T14:46:16Z |
| format | Article |
| id | mit-1721.1/113328 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:46:16Z |
| publishDate | 2018 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1133282022-10-01T22:22:59Z Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors Paletta, Joseph T. Zhang, Hui Boska, Michael D. Ottaviani, M. Francesca Rajca, Andrzej Nguyen, Hung VanThanh Chen, Qixian Harvey, Peter Jiang, Yivan Jasanoff, Alan Pradip Johnson, Jeremiah A. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Laboratory for Nuclear Science Nguyen, Hung VanThanh Chen, Qixian Harvey, Peter Jiang, Yivan Jasanoff, Alan Pradip Johnson, Jeremiah A. Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field ¹H MRI techniques. National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant 1R21EB018529-01A1) National Institutes of Health (U.S.) (Grant U01-NS090451) 2018-01-29T18:42:35Z 2018-01-29T18:42:35Z 2017-07 2017-06 2018-01-29T17:46:02Z Article http://purl.org/eprint/type/JournalArticle 2374-7943 2374-7951 http://hdl.handle.net/1721.1/113328 Nguyen, Hung V.-T. et al. “Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors.” ACS Central Science 3, 7 (July 2017): 800–811 © 2017 American Chemical Society https://orcid.org/0000-0002-6945-4057 https://orcid.org/0000-0002-8163-7059 https://orcid.org/0000-0002-2834-6359 https://orcid.org/0000-0001-9157-6491 http://dx.doi.org/10.1021/ACSCENTSCI.7B00253 ACS Central Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Paletta, Joseph T. Zhang, Hui Boska, Michael D. Ottaviani, M. Francesca Rajca, Andrzej Nguyen, Hung VanThanh Chen, Qixian Harvey, Peter Jiang, Yivan Jasanoff, Alan Pradip Johnson, Jeremiah A. Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors |
| title | Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors |
| title_full | Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors |
| title_fullStr | Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors |
| title_full_unstemmed | Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors |
| title_short | Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors |
| title_sort | nitroxide based macromolecular contrast agents with unprecedented transverse relaxivity and stability for magnetic resonance imaging of tumors |
| url | http://hdl.handle.net/1721.1/113328 https://orcid.org/0000-0002-6945-4057 https://orcid.org/0000-0002-8163-7059 https://orcid.org/0000-0002-2834-6359 https://orcid.org/0000-0001-9157-6491 |
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