Pharmacokinetics and metabolic fate of two nitroxides potentially useful as contrast agents for magnetic resonance imaging.

Paramagnetic nitroxyl-containing compounds have been useful as contrast agents in magnetic resonance imaging (MRI) experiments in animals. Preliminary information on the metabolic fate, pharmacokinetic behavior, stability in tissues, and chemical reduction of two prototypic nitroxides, PCA and TES, is presented. In the dog TES was eliminated more rapidly than PCA. More than 80 % of the dose of both nitroxides was recovered in urine within 6 hours. Nitroxides were reduced in vivo to their corresponding hydroxylamines. No other metabolite was observed. Measured reducing activity in tissue homogenates was greater in liver or kidney than in brain, lung or heart. In each tissue PCA was more stable than TES. PCA was also more resistant to reduction by ascorbic acid at physiologic pH. These preliminary results favor the use of PCA, a pyrrolidinyl nitroxide, over TES, a piperidinyl nitroxide, for MRI contrast enhancement.