Department of Obstetrics and Gynecology, Texas Childrens Hospital, 6621 Fannin Street, Houston, TX 77030, USA.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Sci Rep. 2016 Jun 14;6:27863. doi: 10.1038/srep27863.
The trans-placental permeability of liposomal Gadolinium (Gd) nanoparticle contrast agents was evaluated in a pregnant mouse model. Pregnant Balb/c mice at 16.5 (±1) days of gestation were imaged using a 3D Spoiled Gradient Echo method at 9.4 T using two contrast agents: a clinically approved Gd chelate, Multihance(®) (gadobenate dimeglumine), and a novel experimental liposomal Gd agent. A Dynamic Contrast Enhancement (DCE) protocol was used to capture the dynamics of contrast entry and distribution in the placenta, and clearance from circulation. A blinded clinical radiologist evaluated both sets of images. A reference region model was used to measure the placental flow and physiological parameters; volume transfer constant (K(trans)), efflux rate constant (K(ep)). The Gd content of excised placentae and fetuses was measured, using inductively coupled plasma mass spectrometry (ICP-MS). MRI images of pregnant mice and ICP-MS analyses of placental and fetal tissue demonstrated undetectably low transplacental permeation of the liposomal Gd agent, while the clinical agent (Multihance) avidly permeated the placental barrier. Image interpretation and diagnostic quality was equivalent between the two contrast agents. Additional testing to determine both maternal and fetal safety of liposomal Gd is suggested.
在妊娠小鼠模型中评估了脂质体钆(Gd)纳米颗粒造影剂的胎盘通透性。在 9.4T 下使用 3D Spoiled Gradient Echo 方法对妊娠 16.5(±1)天的 Balb/c 小鼠进行成像,使用两种造影剂:一种是临床批准的 Gd 螯合物,Multihance(®)(钆贝葡胺),另一种是新型实验性脂质体 Gd 试剂。使用动态对比增强(DCE)方案来捕获对比剂进入胎盘和分布以及从循环中清除的动力学。一位盲法临床放射科医生评估了两组图像。使用参考区域模型来测量胎盘的血流和生理参数;容积转移常数(K(trans)),流出率常数(K(ep))。使用电感耦合等离子体质谱法(ICP-MS)测量离体胎盘和胎儿的 Gd 含量。妊娠小鼠的 MRI 图像和胎盘组织及胎儿组织的 ICP-MS 分析表明,脂质体 Gd 试剂的胎盘通透性可检测到低,而临床试剂(Multihance)则强烈渗透胎盘屏障。两种造影剂的图像解释和诊断质量相当。建议进一步测试以确定脂质体 Gd 的母体和胎儿安全性。