Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States.
J Med Chem. 2011 Apr 14;54(7):2331-40. doi: 10.1021/jm101489w. Epub 2011 Mar 10.
Myelination represents one of the most fundamental biological processes in the vertebrate nervous system. Abnormalities and changes in myelination in the central nervous system (CNS) are seen in many neurodegenerative disorders, such as multiple sclerosis (MS). A long-standing goal has been to directly detect and quantify myelin content in order to facilitate diagnosis and therapeutic treatments of myelin-related diseases. In the course of our studies, we have developed a series of small-molecule probes (SMP) as myelin-imaging agents. Among them are coumarin derivatives, which exhibit promising brain permeability and myelin-binding properties. Herein we report a full account of the design and synthesis of coumarin-based SMPs as myelin-imaging agents. Systematic evaluation of these SMPs in both the CNS and peripheral nervous system (PNS) allowed us to identify some lead agents for potential use as fluorescent dyes for intraoperative nerve mapping in surgical operations or as radiotracers for positron emission tomography (PET) imaging of myelination.
髓鞘形成是脊椎动物神经系统中最基本的生物学过程之一。中枢神经系统（CNS）中的髓鞘异常和变化可见于许多神经退行性疾病，如多发性硬化症（MS）。长期以来，人们一直致力于直接检测和定量髓鞘含量，以促进与髓鞘相关疾病的诊断和治疗。在我们的研究过程中，我们开发了一系列小分子探针（SMP）作为髓鞘成像剂。其中包括香豆素衍生物，它们表现出有希望的脑通透性和髓鞘结合特性。在此，我们报告了作为髓鞘成像剂的香豆素基 SMP 的设计和合成的完整说明。对这些 SMP 在中枢神经系统和周围神经系统（PNS）中的系统评估使我们能够确定一些潜在的用于术中神经定位的荧光染料的先导剂，或用于正电子发射断层扫描（PET）成像的放射性示踪剂髓鞘化。
