Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates
Abstract This study aimed to evaluate [18F]GSK1482160 Positron emission tomography imaging for targeting P2X7R, a biomarker for neuroinflammation. Studies of acute neuroinflammation in rodents and transgenic mice with Alzheimer's disease (AD), as well as wild‐type (WT) controls, were conducted...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Brain-X |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/brx2.55 |
| _version_ | 1827299948244238336 |
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| author | Yifan Qiu Lei Bi Guolong Huang Zhijun Li Huiyi Wei Guocong Li Junjie Wei Kai Liao Min Yang Peizhen Ye Yongshan Liu Xianxian Zhao Yuyi Hou Yanfang Shen Renwei Zhou Tuoen Liu Henry Hoi Yee Tong Lu Wang Hongjun Jin |
| author_facet | Yifan Qiu Lei Bi Guolong Huang Zhijun Li Huiyi Wei Guocong Li Junjie Wei Kai Liao Min Yang Peizhen Ye Yongshan Liu Xianxian Zhao Yuyi Hou Yanfang Shen Renwei Zhou Tuoen Liu Henry Hoi Yee Tong Lu Wang Hongjun Jin |
| author_sort | Yifan Qiu |
| collection | DOAJ |
| description | Abstract This study aimed to evaluate [18F]GSK1482160 Positron emission tomography imaging for targeting P2X7R, a biomarker for neuroinflammation. Studies of acute neuroinflammation in rodents and transgenic mice with Alzheimer's disease (AD), as well as wild‐type (WT) controls, were conducted via PET‐CT‐MRI scans after tail vein injection of [18F]GSK1482160. Imaging was quantified based on the time‐activity curve, the standardized uptake value ratio, and the binding kinetics distribution volume ratio (DVR) to assess the expression of P2X7R. Tissues were collected post‐PET for immunofluorescence staining. Correlation analysis was performed between DVR and Morris water maze test results. Finally, dynamic Positron Emission Tomography‐Magnetic Resonance Imaging (PET‐MRI) scans were performed in healthy non‐human primates (NHPs). Our study demonstrated that AD mice had a significantly higher DVR than WT mice in the hippocampus (0.92 ± 0.06 vs. 0.79 ± 0.02, p < 0.05), cortex (1.09 ± 0.03 vs. 0.88 ± 0.04, p < 0.05), and striatum (1.02 ± 0.10 vs. 0.83 ± 0.1, p < 0.05). Immunofluorescence staining showed increased expression of P2X7R in the AD, along with its colocalization with activated microglia and astrocytes. Correlation analysis indicated that brain regions with higher binding of [18F]GSK1482160 (i.e., the cortex, striatum, and hippocampus) were more vulnerable to cognitive impairment. PET‐MRI scans of healthy NHPs demonstrated the feasibility of brain penetration and P2X7R target engagement for the translation of [18F]GSK1482160 in human studies. |
| first_indexed | 2024-04-24T15:42:19Z |
| format | Article |
| id | doaj.art-fb300eb4003343d5bf488965e559c9bf |
| institution | Directory Open Access Journal |
| issn | 2835-3153 |
| language | English |
| last_indexed | 2024-04-24T15:42:19Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain-X |
| spelling | doaj.art-fb300eb4003343d5bf488965e559c9bf2024-04-01T19:00:05ZengWileyBrain-X2835-31532024-03-0121n/an/a10.1002/brx2.55Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primatesYifan Qiu0Lei Bi1Guolong Huang2Zhijun Li3Huiyi Wei4Guocong Li5Junjie Wei6Kai Liao7Min Yang8Peizhen Ye9Yongshan Liu10Xianxian Zhao11Yuyi Hou12Yanfang Shen13Renwei Zhou14Tuoen Liu15Henry Hoi Yee Tong16Lu Wang17Hongjun Jin18Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaCenter of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT‐MRI Center The First Affiliated Hospital of Jinan University Guangzhou Guangdong ChinaCenter of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT‐MRI Center The First Affiliated Hospital of Jinan University Guangzhou Guangdong ChinaCenter of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT‐MRI Center The First Affiliated Hospital of Jinan University Guangzhou Guangdong ChinaCenter of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT‐MRI Center The First Affiliated Hospital of Jinan University Guangzhou Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaDepartment of Biomedical Sciences West Virginia School of Osteopathic Medicine Lewisburg West Virginia USAFaculty of Health Sciences and Sports Macao Polytechnic University Macao SAR ChinaCenter of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT‐MRI Center The First Affiliated Hospital of Jinan University Guangzhou Guangdong ChinaGuangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai Guangdong ChinaAbstract This study aimed to evaluate [18F]GSK1482160 Positron emission tomography imaging for targeting P2X7R, a biomarker for neuroinflammation. Studies of acute neuroinflammation in rodents and transgenic mice with Alzheimer's disease (AD), as well as wild‐type (WT) controls, were conducted via PET‐CT‐MRI scans after tail vein injection of [18F]GSK1482160. Imaging was quantified based on the time‐activity curve, the standardized uptake value ratio, and the binding kinetics distribution volume ratio (DVR) to assess the expression of P2X7R. Tissues were collected post‐PET for immunofluorescence staining. Correlation analysis was performed between DVR and Morris water maze test results. Finally, dynamic Positron Emission Tomography‐Magnetic Resonance Imaging (PET‐MRI) scans were performed in healthy non‐human primates (NHPs). Our study demonstrated that AD mice had a significantly higher DVR than WT mice in the hippocampus (0.92 ± 0.06 vs. 0.79 ± 0.02, p < 0.05), cortex (1.09 ± 0.03 vs. 0.88 ± 0.04, p < 0.05), and striatum (1.02 ± 0.10 vs. 0.83 ± 0.1, p < 0.05). Immunofluorescence staining showed increased expression of P2X7R in the AD, along with its colocalization with activated microglia and astrocytes. Correlation analysis indicated that brain regions with higher binding of [18F]GSK1482160 (i.e., the cortex, striatum, and hippocampus) were more vulnerable to cognitive impairment. PET‐MRI scans of healthy NHPs demonstrated the feasibility of brain penetration and P2X7R target engagement for the translation of [18F]GSK1482160 in human studies.https://doi.org/10.1002/brx2.55[18F]GSK1482160Alzheimer's diseaseneuroinflammationP2X7Rpositron emission tomography |
| spellingShingle | Yifan Qiu Lei Bi Guolong Huang Zhijun Li Huiyi Wei Guocong Li Junjie Wei Kai Liao Min Yang Peizhen Ye Yongshan Liu Xianxian Zhao Yuyi Hou Yanfang Shen Renwei Zhou Tuoen Liu Henry Hoi Yee Tong Lu Wang Hongjun Jin Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates Brain-X [18F]GSK1482160 Alzheimer's disease neuroinflammation P2X7R positron emission tomography |
| title | Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates |
| title_full | Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates |
| title_fullStr | Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates |
| title_full_unstemmed | Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates |
| title_short | Positron emission tomography imaging of the P2X7 receptor with a novel tracer, [18F]GSK1482160, in a transgenic mouse model of Alzheimer's disease and healthy non‐human primates |
| title_sort | positron emission tomography imaging of the p2x7 receptor with a novel tracer 18f gsk1482160 in a transgenic mouse model of alzheimer s disease and healthy non human primates |
| topic | [18F]GSK1482160 Alzheimer's disease neuroinflammation P2X7R positron emission tomography |
| url | https://doi.org/10.1002/brx2.55 |
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