Nitroxide radical contrast agents for safe magnetic resonance imaging: progress, challenges, and perspectives

Magnetic resonance imaging (MRI) is considered one of the most valuable diagnostic technologies in the 21st century. To enhance the image contrast of anatomical features, MRI contrast agents have been widely used in clinical MRI diagnosis, especially those based on gadolinium, manganese, and iron oxide. However, these metal-based MRI contrast agents show potential toxicity to patients, which urges researchers to develop novel MRI contrast agents that can replace metal-based MRI contrast agents. Metal-free nitroxide radical contrast agents (NRCAs) effectively overcome the shortcomings of metal-based contrast agents and also have many advantages, including good biocompatibility, prolonged systemic circulation time, and easily functionalized structures. Importantly, since NRCAs acquire MRI signals with standard tissue water ¹H relaxation mechanisms, they have great potential to realize clinical translation among many metal-free MRI contrast agents. At present, NRCAs have been proposed as an effective substitute for metal-based MRI contrast agents. Herein, this review first briefly introduces NRCAs, including their composition, classification, mechanism of action, application performances and advantages. Then, this review highlights the progress of NRCAs, including small molecule-based NRCAs and polymer-based NRCAs. Finally, this review also discusses the challenges and future perspectives of NRCAs.