Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors
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acscentsci.7b00253.pdf
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Author(s)
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
Date Issued
July 2017
Journal
ACS Central Science
Publisher
American Chemical Society (ACS)
Citation
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
Version
Final published version
Abstract
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.
MIT Department
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
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DOI of Published Version
https://doi.org/10.1021/ACSCENTSCI.7B00253
