Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), Université Paris-Saclay, Orsay 91401, France.
J Med Chem. 2023 Jun 22;66(12):8030-8042. doi: 10.1021/acs.jmedchem.3c00325. Epub 2023 Jun 8.
Positron emission tomography (PET) imaging of the myelin sheath is a powerful tool to investigate multiple sclerosis, monitor its evolution, and support drug development. Radiotracers based on -dimethylaminostilbene (MeDAS) fluorinated analogs have been designed for myelin PET imaging but were never translated to humans. We have synthesized three original fluorinated analogs of MeDAS with low metabolic rates for which binding to myelin in a healthy rat brain was demonstrated by fluorescence microscopy. A tosyl precursor was synthesized for the lead compound PEGMeDAS and automated fluorine-18 radiolabeling afforded [F]PEGMeDAS in 25 ± 5% radiochemical yield and 102 ± 15 GBq/μmol molar activity. Biodistribution in healthy rats demonstrated the brain penetration with low penetration of radiometabolites. However, to isomerization observed in plasma hampers further investigations of this family of molecules and requires complementary data on the behavior of the isomer.
正电子发射断层扫描（PET）成像的髓鞘是一个强大的工具，用于研究多发性硬化症，监测其演变，并支持药物开发。基于 -二甲基氨基二苯乙烯（MeDAS）氟化类似物的示踪剂已被设计用于髓鞘 PET 成像，但从未在人类中转化。我们合成了三种原始的 MeDAS 氟化类似物，其代谢率较低，通过荧光显微镜证明了它们在健康大鼠大脑中的髓鞘结合。为先导化合物 PEGMeDAS 合成了 tosyl 前体，自动化氟-18 放射性标记得到了 [F]PEGMeDAS，放射化学产率为 25±5%，摩尔放射性活度为 102±15GBq/μmol。在健康大鼠中的生物分布表明存在脑穿透，但放射性代谢物的低穿透会妨碍对这类分子的进一步研究，需要关于 异构体行为的补充数据。
