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

作者：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

来源：ACS Central Science, 2017, 3(7): 800-811.

DOI：10.1021/acscentsci.7b00253

Metal-free magnetic resonance imaging (MRI)
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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 nano-architectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to similar 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 H-1 MRI techniques.

• 出版日期2017-7-26