An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis
Abstract Background Angiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, 18F-for-Cl (18F/Cl) exchange s...
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SpringerOpen
2024-12-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-024-00316-5 |
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| author | Pan Zhou Kai Ning Shuai Xue Qingqing Li Danni Li Haijun Yang Zeying Liang Rou Li Jian Yang Xiao Li Lan Zhang |
| author_facet | Pan Zhou Kai Ning Shuai Xue Qingqing Li Danni Li Haijun Yang Zeying Liang Rou Li Jian Yang Xiao Li Lan Zhang |
| author_sort | Pan Zhou |
| collection | DOAJ |
| description | Abstract Background Angiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, 18F-for-Cl (18F/Cl) exchange scheme was designed for the preparation of 18F-labeled MLN-4760, and its targeting ability was investigated in a humanized ACE2 mouse model. Results A novel 18F-labeled MLN-4760 radioligand, abbreviated as 18F-MLN-4760, was successfully synthesized by the 18F/Cl exchange-labeling, and was purified by SepPak C18 columns with a radiochemical yield of 30% and a radiochemical purity of 29.89%. Target distribution of 18F-MLN-4760 in several organs with high ACE2 expression was observed by PET imaging with good stability over 120 min. The biodistribution data showed that the uptake of 18F-MLN-4760 in ACE2-overexpressing organs and tissues was highly specific, and immunohistochemistry confirmed the same results of ACE2 expression and biodistribution in the major organs (heart, liver, lungs, and kidneys). There was a good correlation between the uptake in the organs with high ACE2 expression and ACE2 expression levels (r = 0.935). Conclusion 18F-MLN-4760 was successfully synthesized via 18F/Cl exchange under phase transfer catalysis, and served as a potential probe for ACE2-targeted PET imaging. |
| format | Article |
| id | doaj-art-468e2eb0332941ad8b5f9c7f213eecf9 |
| institution | Kabale University |
| issn | 2365-421X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-468e2eb0332941ad8b5f9c7f213eecf92024-12-08T12:50:00ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2024-12-019111110.1186/s41181-024-00316-5An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysisPan Zhou0Kai Ning1Shuai Xue2Qingqing Li3Danni Li4Haijun Yang5Zeying Liang6Rou Li7Jian Yang8Xiao Li9Lan Zhang10Department of Nuclear Medicine, Shanghai Changhai HospitalArtery PharmaceuticalsShanghai Institute of Applied Physics, Chinese Academy of SciencesArtery PharmaceuticalsDepartment of Nuclear Medicine, Shanghai Changhai HospitalSchool of Medicine, Shanghai UniversitySchool of Medicine, Shanghai UniversityDepartment of Nuclear Medicine, Shanghai Changhai HospitalSchool of Medicine, Shanghai UniversityDepartment of Nuclear Medicine, Shanghai Changhai HospitalShanghai Institute of Applied Physics, Chinese Academy of SciencesAbstract Background Angiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, 18F-for-Cl (18F/Cl) exchange scheme was designed for the preparation of 18F-labeled MLN-4760, and its targeting ability was investigated in a humanized ACE2 mouse model. Results A novel 18F-labeled MLN-4760 radioligand, abbreviated as 18F-MLN-4760, was successfully synthesized by the 18F/Cl exchange-labeling, and was purified by SepPak C18 columns with a radiochemical yield of 30% and a radiochemical purity of 29.89%. Target distribution of 18F-MLN-4760 in several organs with high ACE2 expression was observed by PET imaging with good stability over 120 min. The biodistribution data showed that the uptake of 18F-MLN-4760 in ACE2-overexpressing organs and tissues was highly specific, and immunohistochemistry confirmed the same results of ACE2 expression and biodistribution in the major organs (heart, liver, lungs, and kidneys). There was a good correlation between the uptake in the organs with high ACE2 expression and ACE2 expression levels (r = 0.935). Conclusion 18F-MLN-4760 was successfully synthesized via 18F/Cl exchange under phase transfer catalysis, and served as a potential probe for ACE2-targeted PET imaging.https://doi.org/10.1186/s41181-024-00316-5MLN−4760ACE218F/Cl exchangePET imaging agentPhase transfer catalysis |
| spellingShingle | Pan Zhou Kai Ning Shuai Xue Qingqing Li Danni Li Haijun Yang Zeying Liang Rou Li Jian Yang Xiao Li Lan Zhang An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis EJNMMI Radiopharmacy and Chemistry MLN−4760 ACE2 18F/Cl exchange PET imaging agent Phase transfer catalysis |
| title | An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis |
| title_full | An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis |
| title_fullStr | An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis |
| title_full_unstemmed | An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis |
| title_short | An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis |
| title_sort | ace2 pet imaging agent derived from 18f cl exchange of mln 4760 under phase transfer catalysis |
| topic | MLN−4760 ACE2 18F/Cl exchange PET imaging agent Phase transfer catalysis |
| url | https://doi.org/10.1186/s41181-024-00316-5 |
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