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.

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