PRECLINICAL EVALUATION OF THE PHARMACOKINETICS, BIODISTRIBUTION, AND ELIMINATION OF MS-325, A BLOOD-POOL AGENT FOR MAGNETIC-RESONANCE-IMAGING

RATIONALE AND OBJECTIVES. The authors evaluate MS-325, a new albumin-t argeted magnetic resonance imaging (MRI) contrast agent, for its pharm acokinetics, biodistribution, and elimination characteristics in multi ple 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 w ere determined using gadolinium-153-labeled MS-325 and gamma counting or by using nonlabeled MS-325 and inductively coupled plasma atomic em ission 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 (V-d) values, 0.11 to 0.14 L/kg, and a long elimination half-life (T-e1/2), 2 to 3 hours. Some dose-dep endence 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 bi liary excretion, a larger V-d value, and a shorter T-e1/2. CONCLUSIONS . The pharmacokinetics and elimination profile of MS-325, including va scular retention and renal excretion, are favorable for use in humans as an intravascular contrast agent for MRI.