Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord.
Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord.
复制标题
纵向正电子发射断层扫描成像用于监测脊髓髓磷脂修复。
DOI：
10.1002/ana.23965
复制
发表时间：
2013
影响因子：
11.2
通讯作者：
Wang,Yanming
中科院分区：
文献类型：
--
作者：
Wu,Chunying;Zhu,Junqing;Baeslack,Jonathan;Zaremba,Anita;Hecker,Jordan;Kraso,Janet;Matthews,PaulM;Miller,RobertH;Wang,Yanming
针对髓鞘修复的新型治疗干预措施目前正在开发中，用于多发性硬化症患者的神经保护和功能恢复。然而，髓磷脂修复治疗的发展需要一种非侵入性的方法来测量髓磷脂含量的变化在体内的定量方式还不可能使用磁共振成像。出于这个原因，我们开发了一种新的正电子发射断层扫描（PET）探针，称为[11 C]MeDAS，这是能够纵向成像中枢神经系统髓鞘contents.MethodsThe结合性能的[11 C]MeDAS髓鞘进行了系统的评价，在体外和原位荧光染色的脊髓和大脑，并在体内竞争性阻断研究。在3种大鼠模型中进行了纵向PET研究，包括脑中的急性局灶性神经炎症、脊髓中溶血磷脂酰胆碱（LPC）诱导的局灶性脱髓鞘和实验性自身免疫性脑脊髓炎（EAE）。使用基于间充质干细胞的肝细胞生长因子（HGF）在LPC大鼠模型中进行图像引导的髓鞘修复治疗。[11 C]MeDAS的生物分布和急性毒性研究也carried.ResultsMeDAS选择性染色髓鞘在脊髓和大脑。只要髓鞘保持完整，神经炎症不会影响脑中[11 C]MeDAS的摄取。LPC和EAE大鼠模型中的纵向PET研究表明，[11 C]MeDAS摄取变化与脊髓中相关的髓鞘丢失相关。此外，使用[11 C] MeDAS-PET，在体内纵向监测HGF对髓鞘修复治疗的疗效。解释[11 C] MeDAS-PET是一种有前途的成像标记物，可用于监测体内髓鞘病变，其未来在人类中的应用应该是可以实现的。《神经病学年鉴》2013;74：688-698
ObjectiveNovel therapeutic interventions aimed at myelin repair are now under development for neuroprotection as well as functional recovery of patients with multiple sclerosis. However, development of myelin repair therapy necessitates a noninvasive approach for measuring changes in myelin content in vivo in a quantitative fashion not yet possible using magnetic resonance imaging. For this reason, we developed a novel positron emission tomography (PET) probe, termed [11C]MeDAS, that is capable of longitudinally imaging central nervous system myelin content.MethodsThe binding properties of [11C]MeDAS for myelin were systematically evaluated by in vitro and in situ fluorescent staining of the spinal cord and the brain, and by in vivo competitive blocking studies. Longitudinal PET studies were conducted in 3 rat models involving acute focal neuroinflammation in the brain, lysophosphatidylcholine (LPC)‐induced focal demyelination in the spinal cord, and experimental autoimmune encephalomyelitis (EAE). Image‐guided myelin repair therapy was conducted in an LPC rat model using a mesenchymal stem cell‐based hepatocyte growth factor (HGF). Biodistribution and acute toxicity studies of [11C]MeDAS were also conducted.ResultsMeDAS selectively stains myelin in the spinal cord and brain. Neuroinflammation did not affect [11C]MeDAS uptake in the brain as long as the myelin sheaths remained intact. Longitudinal PET studies in LPC and EAE rat models demonstrate that [11C]MeDAS uptake changes correlate with associated myelin loss in the spinal cord. Furthermore, using [11C]MeDAS‐PET, the efficacy of myelin repair therapy with HGF was longitudinally monitored in vivo.Interpretation[11C]MeDAS‐PET is a promising imaging marker for monitoring myelin pathology in vivo, future applications of which in humans should be achievable. Ann Neurol 2013;74:688–698