Qixian Chen: https://orcid.org/0000-0002-3091-671X
M. Francesca Ottaviani: https://orcid.org/0000-0002-4681-4718
Andrzej Rajca: https://orcid.org/0000-0002-8856-1536
Jeremiah A. Johnson: https://orcid.org/0000-0001-9157-6491
Date of this Version
ACS Cent. Sci. 2017, 3, 800−811
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