¹⁸F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation.

IF 3.1 3区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

EJNMMI Research Pub Date : 2024-01-22 DOI:10.1186/s13550-024-01067-9

Yong-Il Kim, Seung Hak Lee, Jin Hwa Jung, Seog-Young Kim, Nare Ko, Sang Ju Lee, Seung Jun Oh, Jin-Sook Ryu, Dabin Ko, Won Kim, Kyunggon Kim

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引用次数: 0

Abstract

Background: The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the ¹⁸F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury.

Methods: Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, ¹⁸F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5).

Results: ¹⁸F-ASEM PET/MRI showed significantly increased ¹⁸F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant ¹⁸F-ASEM uptake in the denervated side when compared to the control (P = 0.0796).

Conclusions: Our results suggest that nAChR imaging with ¹⁸F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.

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以α7-烟碱乙酰胆碱受体为靶点的 18F-ASEM PET/MRI 可揭示骨骼肌神经支配。

背景：肌肉神经支配中烟碱乙酰胆碱受体（nAChR）表达的增加被认为与神经损伤后乙酰胆碱电生理超敏感有关。因此，我们研究了 18F-ASEM alpha7-nAChR 靶向放射性示踪剂作为一种新诊断方法的实用性，它可以在坐骨神经损伤小鼠模型中观察骨骼肌神经支配：方法：利用10周大的C57BL/6雄性小鼠。方法：利用 10 周大的 C57BL/6 雄性小鼠，对其进行麻醉，在分割臀肌后切除左侧坐骨神经。去神经支配一周（n = 11）和三周（n = 6）后，采集 18F-ASEM 正电子发射断层扫描/磁共振成像（PET/MRI）。测量了去神经支配侧和控制侧胫骨前肌的最大标准化摄取值（SUVmax）。在一周后，对去神经支配侧和对照组胫骨前肌的平均计数进行了自动放射摄影评估。此外，免疫组化法还用于确定一周后去神经支配侧和对照组胫骨前肌中α7-nAChR阳性区域（n = 6）。此外，还使用甲基乌头碱（MLA，n = 5）进行了阻断研究：结果：18F-ASEM PET/MRI 显示，去神经支配后一周和三周，去神经支配的胫骨前肌相对于对照侧的 18F-ASEM 摄取量明显增加。去神经支配肌肉在一周和三周时的 SUVmax 摄取量明显高于对照组（P = 0.0033 和 0.0277）。通过自显影，去神经支配肌肉的相对摄取量明显高于对照组，免疫组化显示去神经支配肌肉中的α7-nAChR表达明显高于对照组（P = 0.0277）。此外，阻断研究显示，与对照组相比，去神经支配侧没有明显的 18F-ASEM 摄取（P = 0.0796）：我们的研究结果表明，18F-ASEM 的 nAChR 成像具有作为外周神经系统疾病无创诊断方法的潜力。

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

EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-

CiteScore

5.90

自引率

3.10%

发文量

审稿时长

13 weeks

期刊介绍： EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.