Department of Radiology, Case Center for Imaging Research, Division of Radiopharmaceutical Science, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, United States.
J Med Chem. 2013 Feb 28;56(4):1629-40. doi: 10.1021/jm301435z. Epub 2013 Feb 18.
Myelin is a membrane system that fosters nervous impulse conduction in the vertebrate nervous system. Myelin sheath disruption is a common characteristic of several neurodegenerative diseases such as multiple sclerosis (MS) and various leukodystrophies. To date, the diagnosis of MS is obtained using a set of criteria in which MRI observations play a central role. However, because of the lack of specificity for myelin integrity, the use of MRI as the primary diagnostic tool has not yet been accepted. In order to improve MR specificity, we began developing MR probes targeted toward myelin. In this work we describe a new myelin-targeted MR contrast agent, Gd-DODAS, based on a stilbene binding moiety and demonstrate its ability to specifically bind to myelin in vitro and in vivo. We also present evidence that Gd-DODAS generates MR contrast in vivo in T1-weighed images and in T1 maps that correlates to the myelin content.
髓鞘是一种膜系统，促进脊椎动物神经系统中的神经冲动传导。髓鞘破坏是多种神经退行性疾病的共同特征，如多发性硬化症 (MS) 和各种脑白质营养不良。迄今为止，MS 的诊断是使用一组标准获得的，其中 MRI 观察起着核心作用。然而，由于缺乏对髓鞘完整性的特异性，MRI 尚未被用作主要的诊断工具。为了提高 MR 的特异性，我们开始开发针对髓鞘的 MR 探针。在这项工作中，我们描述了一种基于二苯乙烯结合部分的新型髓鞘靶向磁共振对比剂 Gd-DODAS，并证明了它在体外和体内特异性结合髓鞘的能力。我们还提供了证据表明 Gd-DODAS 在体内 T1 加权图像和 T1 图谱中产生与髓鞘含量相关的磁共振对比。
