Preclinical evaluation of the pharmacokinetics, biodistribution, and elimination of MS-325, a blood pool agent for magnetic resonance imaging

Abstract

Rationale and objectives: The authors evaluate MS-325, a new albumin-targeted magnetic resonance imaging (MRI) contrast agent, for its pharmacokinetics, biodistribution, and elimination characteristics in multiple animal species.

Methods: Studies were performed in rats, rabbits, and nonhuman primates at intravenous doses ranging from 0.025 to 0.20 mmol/kg. Concentrations of MS-325 in blood, urine, feces, and organs were determined using gadolinium-153-labeled MS-325 and gamma counting or by using non-labeled MS-325 and inductively coupled plasma atomic emission spectrometry.

Results: In rabbits and nonhuman primates, MS-325 is approximately 85% to 95% bound to serum proteins and, as a result, exhibits low volume of distribution (Vd) values, 0.11 to 0.14 L/kg, and a long elimination half-life (Te1/2), 2 to 3 hours. Some dose-dependence in the parameters is apparent in rabbits. MS-325 is eliminated primarily through the renal system in non-human primates. In contrast, the behavior of MS-325 in rats is different, exhibiting increased biliary excretion, a larger Vd value, and a shorter Te1/2.

Conclusions: The pharmacokinetics and elimination profile of MS-325, including vascular retention and renal excretion, are favorable for use in humans as an intravascular contrast agent for MRI.