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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显像示踪剂。

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

作者信息

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

机构信息

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.

Institute of Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.

出版信息

Nat Biomed Eng. 2025 May;9(5):716-729. doi: 10.1038/s41551-025-01362-3. Epub 2025 Mar 5.

DOI:10.1038/s41551-025-01362-3
PMID:40044816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12092265/
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, [F]fluoroedaravone ([F]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 [F]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 [F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.

摘要

活性氧和氮物种（RONS）在神经退行性变的发病机制中起作用，但无法在中枢神经系统中进行体内RONS检测，这使得抗氧化剂临床试验结果的解读变得复杂。在此，我们报告了一种用于体内氧化应激定量的正电子发射断层扫描（PET）探针[F]氟乙拉西坦（[F]FEDV）的合成与表征。该探针源自抗氧化剂依达拉奉，可穿过血脑屏障并在人血浆中稳定存在。在小鼠中，用[F]FEDV进行PET成像能够在纹状体内注射硝普钠后、光血栓形成导致中风后的大脑中动脉以及患有tau蛋白病的大脑中检测到RONS。当使用动态PET成像结合参数映射时，[F]FEDV-PET对RONS的敏感性能够检测到氧化应激的增加。[F]FEDV-PET可用于在体内纵向定量RONS，并评估抗氧化剂临床研究的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/cbf9877ad327/41551_2025_1362_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/f51f3301d1f4/41551_2025_1362_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/bb827337ab25/41551_2025_1362_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/96fe80f9abc7/41551_2025_1362_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/212ddc4ce5c2/41551_2025_1362_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/cbf9877ad327/41551_2025_1362_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/f51f3301d1f4/41551_2025_1362_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/bb827337ab25/41551_2025_1362_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/96fe80f9abc7/41551_2025_1362_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/212ddc4ce5c2/41551_2025_1362_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f894/12092265/cbf9877ad327/41551_2025_1362_Fig6_ESM.jpg

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