Ryan Miller Davis1, Shingo Matsumoto1, Marcelino Bernardo2,3, Anastasia Sowers1, Ken-Ichiro Matsumoto4, Murali C Krishna1, James B Mitchell1
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States; 2Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States; 3National Cancer Institute-Frederick, Frederick, MD, United States; 4National Institute of Radiological Sciences, Molecular Imaging Center, Chiba, Japan
Nitroxides are a diverse class of organic small molecular weight (170-400 Da) paramagnetic radioprotectors. Because nitroxides are paramagnetic, their pharmacodynamics can be monitored indirectly with MRI. This study uses a 3 Tesla human scanner to measure pharmacodynamics of various nitroxides after tail vein injection in mice. In addition, radioprotection studies of those nitroxides were carried out with 300kVp x-rays in a dose range of 6-12.5 Gy. The results of this study provide invaluable information regarding possible causes of nitroxide toxicity, the relationship between nitroxide pharmacokinetics and radioprotective potency, and healthy tissue and tumor redox status.