Magnetic resonance imaging of organic contrast agents in mice: capturing the whole-body redox landscape.
Nitroxides are a class of stable free radicals that have several biomedical applications including radioprotection and noninvasive assessment of tissue redox status. For both of these applications, it is necessary to understand the in vivo biodistribution and reduction of nitroxides. In this study, magnetic resonance imaging was used to compare tissue accumulation (concentration) and reduction of two commonly studied nitroxides: the piperidine nitroxide Tempol and the pyrrolidine nitroxide 3-CP. It was found that 3-CP was reduced 3 to 11 times slower (depending on the tissue) than Tempol in vivo and that maximum tissue concentration varies substantially between tissues (0.6-7.2mM). For a given tissue, the maximum concentration usually did not vary between the two nitroxides. Furthermore, using electron paramagnetic resonance spectroscopy, we showed that the nitroxide reduction rate depends only weakly on cellular pO(2) in the oxygen range expected in vivo. These observations, taken with the marked variation in nitroxide reduction rates observed between tissues, suggest that tissue pO(2) is not a major determinant of the nitroxide reduction rate in vivo. For the purpose of redox imaging, 3-CP was shown to be an optimal choice based on the achievable concentrations and bioreduction observed in vivo.
Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA. davisrm2@mail.nih.gov
Ryan M
RM
Davis
Shingo
S
Matsumoto
Marcelino
M
Bernardo
Anastasia
A
Sowers
Ken-Ichiro
K
Matsumoto
Murali C
MC
Krishna
James B
JB
Mitchell
D000818:Animals; D001481:Basal Metabolism; D003287:Contrast Media; D003497:Cyclic N-Oxides / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009589:Nitrogen Oxides / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism*; D013113:Spin Labels; D014407:Tumor Cells, Cultured; D051598:Whole Body Imaging
D003287:Contrast Media; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D011759:Pyrrolidines; D013113:Spin Labels; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; C039900:nitroxyl; D010100:Oxygen; C001803:tempol