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

• Main Authors: Nguyen, Hung V.T., Chen, Qixian, Paletta, Joseph T., Harvey, Peter, Jiang, Yivan, Zhang, Hui, Boska, Michael, Ottaviani, M. Francesca, Jasanoff, Alan, Rajca, Andrzej, Johnson, Jeremiah A.
• Format: Text
• Language: unknown
• Published: DigitalCommons@University of Nebraska - Lincoln 2017
• Subjects: Chemistry; Orca
• Online Access: https://digitalcommons.unl.edu/chemistryrajca/15; https://digitalcommons.unl.edu/context/chemistryrajca/article/1015/viewcontent/NguyenACSCentralScience2017NitroxideBased.pdf; https://digitalcommons.unl.edu/context/chemistryrajca/article/1015/filename/0/type/additional/viewcontent/NguyenACSCentralScience2017NitroxideBased__SUPPL.pdf

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 nitroxidefunctionalized 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. Includes Supplementary material