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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Imaging of CNS myelin by positron-emission tomography
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Imaging of CNS myelin by positron-emission tomography

机译：正电子发射断层扫描显像中枢神经系统髓鞘

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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, MR1 assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2methoxy 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 C-11-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.
机译：促进髓鞘修复是髓鞘疾病领域中最有希望的治疗途径之一。在未来的临床试验中，评估髓鞘再生将需要可靠且可量化的髓磷脂标记物作为替代标记物。迄今为止，MR1评估缺乏评估脑内髓鞘再生水平的特异性。在这里，我们描述了1,4-双（对氨基苯乙烯基）-2甲氧基苯（BMB），这是一种合成的荧光分子，可选择性地与离体和体内髓鞘结合。 BMB与髓磷脂的结合使得能够在脱髓鞘的实验性自身免疫性脑炎模型中检测脱髓鞘的病变，并允许量化在脱髓鞘的突变体中的髓磷脂损失的平均值。在多发性硬化症的大脑中，不同水平的BMB结合使阴影斑块中的髓鞘再生与脱髓鞘病变或正常出现的白质区分开。全身注射后，BMB越过血脑屏障并以剂量依赖性和可逆的方式与髓磷脂结合。最后，我们提供了证据，表明C-11-放射性标记的BMB可以在体内用于通过狒狒中的正电子发射断层扫描成像CNS髓磷脂。我们的结果为通过正电子发射断层扫描技术开发脑髓磷脂成像技术提供了前景。

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