Preclinical evaluation of the pharmacokinetics, biodistribution, and elimination of MS-325, a blood pool agent for magnetic resonance imaging
Preclinical evaluation of the pharmacokinetics, biodistribution, and elimination of MS-325, a blood pool agent for magnetic resonance imaging
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DOI：
10.1097/00004424-199712000-00004
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发表时间：
1997-12-01
影响因子：
6.7
通讯作者：
Lauffer, RB
中科院分区：
文献类型：
--
作者：
Parmelee, DJ;Walovitch, RC;Lauffer, RB
理由和目标。作者评估了 MS-325（一种新型白蛋白靶向磁共振成像 (MRI) 造影剂）在多种动物物种中的药代动力学、生物分布和消除特性。方法。研究在大鼠、兔子和非人灵长类动物中进行，静脉注射剂量范围为 0.025 至 0.20 mmol/kg。使用钆153标记的MS-325和伽马计数或使用未标记的MS-325和电感耦合等离子体原子发射光谱法测定血液、尿液、粪便和器官中MS-325的浓度。 结果。在兔子和非人灵长类动物中，MS-325 大约 85% 至 95% 与血清蛋白结合，因此表现出较低的分布容积 (V-d) 值（0.11 至 0.14 L/kg）和较长的消除半衰期 (T-e1/2)（2 至 3 小时）。在兔子中，参数的一些剂量依赖性是明显的。 MS-325 在非人类灵长类动物中主要通过肾脏系统消除。相反，MS-325在大鼠中的行为有所不同，表现出胆汁排泄增加、V-d值较大和T-e1/2较短。结论。 MS-325 的药代动力学和消除特征（包括血管滞留和肾脏排泄）有利于在人体中用作 MRI 的血管内造影剂。
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 nonlabeled 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 (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-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 V-d value, and a shorter T-e1/2.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.