Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA.
Bioorg Med Chem. 2010 Dec 15;18(24):8592-9. doi: 10.1016/j.bmc.2010.10.018. Epub 2010 Nov 9.
C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct) value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-type mouse brain, a pattern that was also consistently observed in Black-Gold or MBP antibody staining. Ex vivo autoradiography demonstrated that [(11)C]MeDAS readily entered the mouse brain and selectively labeled myelinated regions with high specificity. Biodistribution studies showed abundant initial brain uptake of [(11)C]MeDAS with 2.56% injected dose/whole brain at 5 min post injection and prolonged retention in the brain with 1.37% injected dose/whole brain at 60 min post injection. An in vivo pharmacokinetic profile of [(11)C]MeDAS was quantitatively analyzed through a microPET study in an Plp-Akt-DD hypermyelinated mouse model. MicroPET studies showed that [(11)C]MeDAS exhibited a pharmacokinetic profile that readily correlates the radioactivity concentration to the level of myelination in the brain. These studies suggest that MeDAS is a sensitive myelin probe that provides a direct means to detect myelin changes in the brain. Thus, it can be used as a myelin-imaging marker to monitor myelin pathology in vivo.
C-11 标记的 N-甲基-4,4'-二氨基二苯乙烯 ([(11)C]MeDAS) 被合成并评估为一种用于体内 microPET 成像髓鞘的新型示踪剂。[(11)C]MeDAS 具有最佳的亲脂性，脑摄取的 logP(oct) 值为 2.25。体外和离体染色均显示 MeDAS 在富含髓鞘的区域（如胼胝体和纹状体）积累。在 Plp-Akt-DD 小鼠脑中，MeDAS 可视化的胼胝体区域比野生型小鼠脑中大得多，这一模式在 Black-Gold 或 MBP 抗体染色中也得到了一致的观察。离体放射自显影显示，[(11)C]MeDAS 很容易进入小鼠大脑并选择性地标记富含髓鞘的区域，具有很高的特异性。生物分布研究表明，[(11)C]MeDAS 有大量的初始脑摄取，在注射后 5 分钟时为 2.56%注射剂量/全脑，在注射后 60 分钟时为 1.37%注射剂量/全脑。通过 Plp-Akt-DD 超髓鞘小鼠模型的 microPET 研究对 [(11)C]MeDAS 的体内药代动力学特征进行了定量分析。microPET 研究表明，[(11)C]MeDAS 表现出的药代动力学特征与大脑中髓鞘化水平的放射性浓度密切相关。这些研究表明，MeDAS 是一种敏感的髓鞘探针，可提供一种直接的方法来检测大脑中的髓鞘变化。因此，它可以用作髓鞘成像标志物来监测体内髓鞘病理学。
