Department of Experimental Diagnostic Imaging, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Contrast Media Mol Imaging. 2011 Jul-Aug;6(4):289-97. doi: 10.1002/cmmi.431. Epub 2011 Jan 6.
The purpose of this study was to evaluate poly(L-glutamic acid)-benzyl-DTPA-Gd (PG-Gd), a new biodegradable macromolecular magnetic resonance imaging contrast agent, for its pharmacokinetics and MRI enhancement in nonhuman primates. Studies were performed in rhesus monkeys at intravenous doses of 0.01, 0.02 and 0.08 mmol Gd/kg. T(1)-weighted MR images were acquired at 1.5 T using fast spoiled gradient recalled echo and fast spin echo imaging protocols. The small-molecule contrast agent Magnevist was used as a control. PG-Gd in the monkey showed a bi-exponential disposition. The initial blood concentrations within 2 h of PG-Gd administration were much higher than those for Magnevist. The high blood concentration of PG-Gd was consistent with the MR imaging data, which showed prolonged circulation of PG-Gd in the blood pool. Enhancement of blood vessels and organs with a high blood perfusion (heart, liver, and kidney) was clearly visualized at 2 h after contrast injection at the three doses used. A greater than proportional increase of the area under the blood concentration-time curve was observed when the administered single dose was increased from 0.01 to 0.08 mmol/kg. By 2 days after PG-Gd injection, the contrast agent was mostly cleared from all major organs, including kidney. The mean residence time was 15 h at the 0.08 mmol/kg dose. A similar pharmacokinetic profile was observed in mice, with a mean residence time of 5.4 h and a volume of distribution at steady-state of 85.5 ml/kg, indicating that the drug was mainly distributed in the blood compartment. Based on this pilot study, further investigations on the potential systemic toxicity of PG-Gd in both rodents and large animals are warranted before testing this agent in humans.
本研究旨在评估新型可生物降解高分子磁共振成像对比剂聚（L-谷氨酸）-苄基-DTPA-Gd（PG-Gd）在非人灵长类动物中的药代动力学和 MRI 增强作用。在静脉注射 0.01、0.02 和 0.08mmol Gd/kg 剂量的恒河猴中进行了研究。使用快速扰相梯度回波和快速自旋回波成像方案在 1.5T 上采集 T1 加权磁共振图像。小分子对比剂 Magnevist 用作对照。猴体内的 PG-Gd 呈双指数分布。PG-Gd 给药后 2 小时内的初始血药浓度明显高于 Magnevist。PG-Gd 的高血药浓度与磁共振成像数据一致，表明 PG-Gd 在血池中循环时间延长。在使用三种剂量的对比剂后 2 小时，高血流灌注的血管和器官（心脏、肝脏和肾脏）的增强明显可见。当单次给药剂量从 0.01 增加到 0.08mmol/kg 时，观察到血药浓度-时间曲线下面积呈大于比例的增加。PG-Gd 注射后 2 天，所有主要器官（包括肾脏）中的对比剂基本清除。在 0.08mmol/kg 剂量下，平均停留时间为 15 小时。在小鼠中观察到类似的药代动力学特征，平均停留时间为 5.4 小时，稳态分布容积为 85.5ml/kg，表明药物主要分布在血液隔室中。基于这项初步研究，在人类中测试该药物之前，有必要在啮齿动物和大动物中进一步研究 PG-Gd 的潜在全身毒性。
