Wu Chunying, Wei Jinjun, Tian Donghua, Feng Yue, Miller Robert H, Wang Yanming
Department of Radiology and Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Med Chem. 2008 Nov 13;51(21):6682-8. doi: 10.1021/jm8003637. Epub 2008 Oct 10.
Abnormalities and changes in myelination in the brain are seen in many neurodegenerative disorders such as multiple sclerosis (MS). Direct detection and quantification of myelin content in vivo is desired to facilitate diagnosis and therapeutic treatments of myelin-related diseases. The imaging studies require use of myelin-imaging agents that readily enter the brain and selectively bind to myelinated regions. For this purpose, we have systematically evaluated a series of stilbene derivatives as myelin imaging agents. Spectrophotometry-based and radioligand-based binding assays showed that these stilbene derivatives exhibited relatively high myelin-binding affinities. In vitro myelin staining exhibited that the compounds selectively stained intact myelinated regions in wild type mouse brain. In situ tissue staining demonstrated that the compounds readily entered the mouse brain and selectively labeled myelinated white matter regions. These studies suggested that these stilbene derivatives can be used as myelin-imaging probes to monitor myelin pathology in vivo.
在许多神经退行性疾病如多发性硬化症（MS）中，可观察到大脑中髓鞘形成的异常和变化。为了促进与髓鞘相关疾病的诊断和治疗，需要在体内直接检测和定量髓鞘含量。成像研究需要使用能够轻易进入大脑并选择性结合髓鞘区域的髓鞘成像剂。为此，我们系统地评估了一系列芪衍生物作为髓鞘成像剂。基于分光光度法和基于放射性配体的结合试验表明，这些芪衍生物表现出相对较高的髓鞘结合亲和力。体外髓鞘染色显示，这些化合物能选择性地对野生型小鼠大脑中完整的髓鞘区域进行染色。原位组织染色表明，这些化合物能轻易进入小鼠大脑并选择性标记髓鞘化的白质区域。这些研究表明，这些芪衍生物可作为髓鞘成像探针用于监测体内髓鞘病变。
