Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Chemistry, and Biomedical Engineering, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
ChemMedChem. 2012 Dec;7(12):2194-203. doi: 10.1002/cmdc.201200343. Epub 2012 Nov 7.
Myelination is a fundamental biological process in the vertebrate nervous system. Damage to or malformation of myelin can lead to various neurological diseases; for example, demyelination in the spinal cord is a major cause of paralysis of patients suffering from multiple sclerosis and related diseases. The ability to directly track myelin levels in the spinal cord is needed in order to assess the efficacy of therapeutics in promoting myelin repair. To address this unmet need, 4-((E)-4-((E)-4-aminostyryl)-2,5-dimethoxystyryl)-N-methylaniline, known as Case Imaging Compound (CIC), has been developed as a myelin-targeted fluorescent imaging agent that selectively binds to myelin. CIC was synthesized via an improved route and evaluated as a fluorescent probe for two-photon fluorescent imaging of myelin in the spinal cord in both demyelinated and dysmyelinated models. In vitro and ex vivo tissue staining both suggest that CIC selectively binds to in animal models. Further evaluation in animal models indicated that CIC is sensitive to differences in myelin content in healthy versus pathological myelin. CIC could potentially be useful in the development and evaluation of novel therapies for multiple sclerosis and other demyelinating diseases.
髓鞘形成是脊椎动物神经系统中的一个基本生物学过程。髓鞘的损伤或畸形可导致各种神经疾病；例如，脊髓脱髓鞘是多发性硬化症和相关疾病患者瘫痪的主要原因。为了评估治疗方法促进髓鞘修复的疗效，需要能够直接跟踪脊髓中的髓鞘水平。为了满足这一未满足的需求，开发了一种名为 Case Imaging Compound（CIC）的髓鞘靶向荧光成像剂，作为一种荧光探针，可选择性结合髓鞘。CIC 通过改进的路线合成，并作为脊髓脱髓鞘和发育不良模型中髓鞘的双光子荧光成像的荧光探针进行了评估。体外和离体组织染色均表明 CIC 选择性地结合到动物模型中。在动物模型中的进一步评估表明，CIC 对健康与病理髓鞘之间的髓鞘含量差异敏感。CIC 可能对多发性硬化症和其他脱髓鞘疾病的新型治疗方法的开发和评估有用。
