A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering Pub Date : 2025-03-05 DOI:10.1038/s41551-025-01362-3

Justin H. Wilde, Yu-Yo Sun, Spenser R. Simpson, Ethan R. Hill, Zhongxiao Fu, Emily J. Bian, Melissa M. Kinkaid, Paulina Villanueva, Aden F. Weybright, William R. Terrell, Zoraiz Qureshi, Shashika S. Perera, Heather S. Sheppard, James R. Stone, Bijoy K. Kundu, Chia-Yi Kuan, Kiel D. Neumann

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Abstract

Reactive oxygen and nitrogen species (RONS) contribute to the pathogenesis of neurodegeneration, but the inability to detect RONS in vivo in the central nervous system has confounded the interpretation of results of clinical trials of antioxidants. Here we report the synthesis and characterization of a positron emission tomography (PET) probe, [¹⁸F]fluoroedaravone ([¹⁸F]FEDV), for the in vivo quantification of oxidative stress. Derived from the antioxidant edaravone, the probe can diffuse through the blood–brain barrier and is stable in human plasma. In mice, PET imaging with [¹⁸F]FEDV allowed for the detection of RONS after intrastriatal injection of sodium nitroprusside, in the middle cerebral artery after stroke by photothrombosis, and in brains with tauopathy. When using dynamic PET imaging coupled with parametric mapping, the sensitivity of [¹⁸F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [¹⁸F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.

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一种用于中枢神经系统氧化应激成像的正电子发射断层扫描示踪剂

活性氧和活性氮（RONS）参与神经退行性变的发病机制，但中枢神经系统体内无法检测到活性氧和活性氮，这使得抗氧化剂临床试验结果的解释变得混乱。本文报道了一种正电子发射断层扫描（PET）探针[18F]fluoroedaravone （[18F]FEDV）的合成和表征，用于体内氧化应激的量化。从抗氧化剂依达拉奉中提取的探针可以通过血脑屏障扩散，并且在人血浆中稳定。在小鼠中，使用[18F]FEDV进行PET成像，可以在颅腔内注射硝普钠后、脑卒中后光血栓形成的大脑中动脉和脑病变中检测到ron。当使用动态PET成像与参数映射相结合时，[18F]FEDV-PET对RONS的灵敏度允许检测氧化应激的增加。[18F]FEDV-PET可用于体内纵向量化RONS和评估抗氧化剂临床研究结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Biomedical Engineering Medicine-Medicine (miscellaneous)

CiteScore

45.30

自引率

1.10%

发文量

138

期刊介绍： Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.