Improved synthesis of an ergothioneine PET radioligand for imaging oxidative stress in Alzheimer's disease.
Improved synthesis of an ergothioneine PET radioligand for imaging oxidative stress in Alzheimer's disease.
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DOI：
10.1002/1873-3468.14303
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发表时间：
2022-05
期刊：
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
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L-麦角硫因（ERGO）是一种有效的抗氧化剂，具有细胞保护作用。为了研究ERGO生物分布和检测体内氧化应激，我们报告了一种基于用甲酯保护组氨酸羧基的[11 C]标记的ERGO PET放射性配体的有效且可重复的制备。总的来说，与使用叔丁基酯的先前报道相比，使用甲基酯的这种新的保护方法将4步反应的化学产率从14%提高到24%。前体的[11 C] CH 3甲基化提供具有55 ± 10%放射化学纯度和450 ± 200 TBq/mmol摩尔活性的所需产物。[11 C]ERGO放射性配体能够检测阿尔茨海默病临床前动物模型中氧化应激的阈值水平。L-麦角硫因（ERGO）是一种天然抗氧化剂，能够清除活性氧和过渡金属。这项工作报告了一种新的[11 C]ERGO PET放射性配体的稳健合成，以可视化ERGO的作用。在这里，使用临床前动物模型，我们表明探针可以报告阿尔茨海默病中氧化应激的阈值水平。
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 [11C]-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 [11C]CH3 methylation of the precursor provided the desired product with 55 ± 10% radiochemical purity and a molar activity of 450 ± 200 TBq/mmol. The [11C]ERGO radioligand was able to detect threshold levels of oxidative stress in a preclinical animal model of Alzheimer’s disease. L-Ergothioneine (ERGO) is a natural antioxidant capable of scavenging reactive oxygen species and transition metals. This work reports the robust synthesis of a novel [11C]ERGO PET radioligand to visualize ERGO in action. Here, using the preclinical animal models, we show that the probe could report the threshold levels of oxidative stress in Alzheimer’s disease.