Stankoff Bruno, Wang Yanming, Bottlaender Michel, Aigrot Marie-Stephane, Dolle Frederic, Wu Chunying, Feinstein Douglas, Huang Guo-Feng, Semah Frank, Mathis Chester A, Klunk William, Gould Robert M, Lubetzki Catherine, Zalc Bernard
Institut National de la Santé et de la Recherche Médicale, U711, Hôpital de la Salpêtrière, F-75013 Paris, France.
Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9304-9. doi: 10.1073/pnas.0600769103. Epub 2006 Jun 5.
Promoting myelin repair is one of the most promising therapeutic avenues in the field of myelin disorders. In future clinical trials, evaluation of remyelination will require a reliable and quantifiable myelin marker to be used as a surrogate marker. To date, MRI assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2-methoxy benzene (BMB), a synthesized fluorescent molecule, that binds selectively to myelin both ex vivo and in vivo. The binding of BMB to myelin allows the detection of demyelinating lesions in an experimental autoimmune encephalitis model of demyelination and allows a mean for quantifying myelin loss in dysmyelinating mutants. In multiple sclerosis brain, different levels of BMB binding differentiated remyelination in shadow plaques from either demyelinated lesions or normal-appearing white matter. After systemic injection, BMB crosses the blood-brain barrier and binds to myelin in a dose-dependent and reversible manner. Finally, we provide evidence that (11)C-radiolabeled BMB can be used in vivo to image CNS myelin by positron-emission tomography in baboon. Our results provide a perspective for developing a brain myelin imaging technique by positron-emission tomography.
促进髓鞘修复是髓鞘疾病领域最具前景的治疗途径之一。在未来的临床试验中，对髓鞘再生的评估将需要一种可靠且可量化的髓鞘标记物作为替代标记物。迄今为止，MRI评估在评估脑内髓鞘再生水平方面缺乏特异性。在此，我们描述了一种合成荧光分子1,4-双（对氨基苯乙烯基）-2-甲氧基苯（BMB），它在体外和体内均能选择性地与髓鞘结合。BMB与髓鞘的结合使得在实验性自身免疫性脑脊髓炎脱髓鞘模型中能够检测到脱髓鞘病变，并为量化髓鞘形成异常突变体中的髓鞘损失提供了一种方法。在多发性硬化症患者的大脑中，不同水平的BMB结合区分了阴影斑块中的髓鞘再生与脱髓鞘病变或外观正常的白质。全身注射后，BMB可穿过血脑屏障，并以剂量依赖和可逆的方式与髓鞘结合。最后，我们提供证据表明，（11）C放射性标记的BMB可用于狒狒体内的正电子发射断层扫描成像中枢神经系统髓鞘。我们的结果为开发一种通过正电子发射断层扫描进行脑髓鞘成像技术提供了一个视角。
