Metabolic fate in the dog of the nitroxide moiety in a compound with potential utility as a contrast agent in MRI.
Nitroxides, paramagnetic compounds with demonstrated effectiveness as contrast agents in proton magnetic resonance imaging, shorten the relaxation times of protons and therefore cause an increase in image intensity in tissues into which they distribute. In this study, the metabolic fate of the nitroxide moiety was examined in the dog using a pyrrolidine nitroxide derivative, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, for which contrast-enhancing properties have been previously studied in animals. After radiolabeling by microwave discharge in the presence of tritium gas, the compound was administered intravenously to a dog. Ninety-four percent of the radioactivity injected was recovered in urine within 3 days; the majority (90%) was excreted during the first 6 h. The radioactivity in the urine was identified as either the unchanged nitroxide or its corresponding hydroxylamine. Neither complete reduction of the nitroxide moiety to the amine nor any other metabolic transformation was observed.
Eriksson
U G
UG
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
Ogan
M D
MD
Peng
C T
CT
Brasch
R C
RC
Tozer
T N
TN
D000818:Animals; D001711:Biotransformation; D003287:Contrast Media / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000378:metabolism*; D004285:Dogs; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009589:Nitrogen Oxides / Q000378:metabolism; D013113:Spin Labels
D003287:Contrast Media; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; C032289:2,2,5,5-tetramethyl-1-pyrrolidinyloxy-3-carboxylic acid