Pharmacokinetic properties of nitroxide-labeled albumin in mice

We have conjugated bovine serum albumin (BSA) with a pyrrolidinyl nitroxide and report on the in vivo pharmacokinetic properties of this conjugate in mice. In vivo EPR measurements of nitroxide were obtained after intravenous injection of 30 mg of labeled BSA by analysis of the nitroxide signal from the tails of mice. Following in vivo nitroxide measurements, the animals were sacrificed by exsanguination and organs were removed for determination of nitroxide levels. The level of nitroxide as determined by in vivo measurements declined exponentially with time and had a half-life (t1/2) of 7 hours. Blood nitroxide levels also declined exponentially with time with an initial t1/2 of 70 minutes and a terminal t1/2 of 10 hours. Nitroxide concentration varied among different organs; no nitroxide was detected within brain whereas lung had high concentrations of nitroxide. Liver and kidney both had relatively low levels of oxidized nitroxide, though total nitroxide (reduced plus oxidized) accumulated in the kidneys with time. Nitroxide-labeled BSA was well tolerated by the mice, is relatively stable, and is mainly confined to the intravascular space. Nitroxide-labeled albumin may be useful as a contrast agent for MRI or EPR imaging.