Improved synthesis of an ergothioneine PET radioligand for imaging oxidative stress in Alzheimer's disease. Issue 10 (7th February 2022)

• Record Type: Journal Article
• Authors: Behof, William J.; Whitmore, Clayton A.; Haynes, Justin R.; Rosenberg, Adam J.; Tantawy, Mohammed N.; Peterson, Todd E.; Harrison, Fiona E.; Beelman, Robert B.; Wijesinghe, Printha; Matsubara, Joanne A.; Pham, Wellington
• Is Part Of: FEBS letters. Volume 596:Issue 10(2022)
• Page Start: 1279
• Page End: 1289
• Publication Date: 2022-02-07
• Subjects: alzheimer -- ergothioneine -- inflammation -- oxidative stress -- PET imaging -- ROS; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14303
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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 [ 11 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 [ 11 C]CH3 methylation of the precursor provided the desired product with 55 ± 10% radiochemical purity and a molar activity of 450 ± 200 TBq·mmol −1 . The [ 11 C]ERGO radioligand was able to detect threshold levels of oxidative stress in a preclinical animal model of Alzheimer's disease. Abstract : 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 [ 11 C]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.