18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation
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 radiot...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-01-01
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| Series: | EJNMMI Research |
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| Online Access: | https://doi.org/10.1186/s13550-024-01067-9 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yong-il Kim |
| collection | DOAJ |
| description | 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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| format | Article |
| id | doaj.art-7ea6272d69184eddaebe88a7ea9c8c5d |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-03-07T15:25:49Z |
| publishDate | 2024-01-01 |
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| series | EJNMMI Research |
| spelling | doaj.art-7ea6272d69184eddaebe88a7ea9c8c5d2024-03-05T16:42:59ZengSpringerOpenEJNMMI Research2191-219X2024-01-011411910.1186/s13550-024-01067-918 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervationYong-il Kim0Seung Hak Lee1Jin Hwa Jung2Seog-Young Kim3Nare Ko4Sang Ju Lee5Seung Jun Oh6Jin-Sook Ryu7Dabin Ko8Won Kim9Kyunggon Kim10Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of MedicineConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical CenterConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical CenterDepartment of Nuclear Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Nuclear Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Nuclear Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Nuclear Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of MedicineConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical CenterAbstract 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.https://doi.org/10.1186/s13550-024-01067-9Muscle denervationPeripheral nervous systemNicotinic acetylcholine receptor18F-ASEMPositron emission tomography |
| spellingShingle | 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 18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation EJNMMI Research Muscle denervation Peripheral nervous system Nicotinic acetylcholine receptor 18F-ASEM Positron emission tomography |
| title | 18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation |
| title_full | 18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation |
| title_fullStr | 18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation |
| title_full_unstemmed | 18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation |
| title_short | 18 F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation |
| title_sort | 18 f asem pet mri targeting alpha7 nicotinic acetylcholine receptor can reveal skeletal muscle denervation |
| topic | Muscle denervation Peripheral nervous system Nicotinic acetylcholine receptor 18F-ASEM Positron emission tomography |
| url | https://doi.org/10.1186/s13550-024-01067-9 |
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