Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
FEBS Lett. 2022 May;596(10):1279-1289. doi: 10.1002/1873-3468.14303. Epub 2022 Feb 7.
L-ergothioneine (ERGO) is a potent antioxidant with cytoprotective effects. To study ERGO biodistribution and detect oxidative stress in vivo, we report an efficient and reproducible preparation of [ C]-labeled ERGO PET radioligand based on protecting the histidine carboxylic group with a methyl ester. Overall, this new protection approach using methyl ester improved the chemical yield of a 4-step reaction from 14% to 24% compared to the previous report using t-butyl ester. The [ C]CH methylation of the precursor provided the desired product with 55 ± 10% radiochemical purity and a molar activity of 450 ± 200 TBq·mmol . The [ C]ERGO radioligand was able to detect threshold levels of oxidative stress in a preclinical animal model of Alzheimer's disease.
L-ergothioneine (ERGO) 是一种具有细胞保护作用的强效抗氧化剂。为了研究 ERGO 的生物分布并在体内检测氧化应激，我们报告了一种基于用甲酯保护组氨酸羧酸基团的高效且可重现的 [C]-标记 ERGO PET 放射性配体的制备方法。总的来说，与之前使用叔丁酯的报告相比，这种使用甲酯的新保护方法将 4 步反应的总化学产率从 14%提高到了 24%。前体的 [C]CH 甲基化提供了所需产物，放射化学纯度为 55±10%，摩尔活度为 450±200TBq·mmol -1 。[C]ERGO 放射性配体能够检测到阿尔茨海默病临床前动物模型中氧化应激的阈值水平。
