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

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

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49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)800-811
Number of pages12
JournalACS Central Science
Volume3
Issue number7
DOIs
StatePublished - Jul 26 2017

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ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Nguyen, H. V. T., Chen, Q., Paletta, J. T., Harvey, P., Jiang, Y., Zhang, H., Boska, M. D., Ottaviani, M. F., Jasanoff, A., Rajca, A., & 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