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Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors

Nguyen, Hung V.-T.; Chen, Qixian; Paletta, Joseph T.; Harvey, Peter; Jiang, Yivan; Zhang, Hui; Boska, Michael D.; Ottaviani, M. Francesca; Jasanoff, Alan; Rajca, Andrzej; Johnson, Jeremiah A.

Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors Thumbnail


Authors

Hung V.-T. Nguyen

Qixian Chen

Joseph T. Paletta

Yivan Jiang

Hui Zhang

Michael D. Boska

M. Francesca Ottaviani

Alan Jasanoff

Andrzej Rajca

Jeremiah A. Johnson



Abstract

© 2017 American Chemical Society. 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.

Citation

Nguyen, H. V., Chen, Q., Paletta, J. T., Harvey, P., Jiang, Y., Zhang, H., …Johnson, J. A. (2017). Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors. ACS Central Science, 3(7), 800-811. https://doi.org/10.1021/acscentsci.7b00253

Journal Article Type Article
Acceptance Date Jun 14, 2017
Online Publication Date Jul 12, 2017
Publication Date Jul 26, 2017
Deposit Date Oct 23, 2019
Publicly Available Date Jan 21, 2020
Journal ACS Central Science
Electronic ISSN 2374-7951
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 3
Issue 7
Pages 800-811
DOI https://doi.org/10.1021/acscentsci.7b00253
Public URL https://nottingham-repository.worktribe.com/output/2829169
Publisher URL https://pubs.acs.org/doi/10.1021/acscentsci.7b00253

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