Nitroxides as Cancer Imaging Agents

Ryan      M. Davis; James      B. Mitchell; Murali      C. Krishna

Abstract

Nitroxides are low molecular weight (150-400 Da) superoxide dismutase mimics that exhibit antioxidant, radical scavenging, and radioprotective activity. Additionally, the paramagnetic nature of nitroxides makes them viable as both spin probes for electron paramagnetic resonance imaging as well as contrast agents for magnetic resonance imaging. These imaging techniques enable in vivo monitoring of nitroxide metabolism. In biological systems, nitroxide metabolism occurs predominantly via reduction of the nitroxide to a hydroxylamine. The rate of nitroxide reduction can increase or decrease due to oxidative stress, suggesting that nitroxides can provide an imaging-based assay of tissue redox status. The current review briefly summarizes the potential clinical applications of nitroxides, and focuses on the biochemical and tumor microenvironmental factors that affect the rate of nitroxide reduction. The potential therapeutic applications and bio-reduction mechanisms are discussed in the context of their relevance to oncology.

Keywords: Nitroxides, oxidative stress, redox-imaging, magnetic resonance imaging, electron paramagnetic resonance, radioprotective potencies, protonated superoxide, penicillamine, cystine, ionizing radiation, radicals, electron paramagnetic resonance spectroscopy, gradient magnets, OMRI, SCCVII tumors