Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020
Abstract Background [11C]TGN-020 has been developed as a positron emission tomography (PET) tracer for imaging aquaporin-4 (AQP4) in the brain and used in clinical studies. Previously, [11C]TGN-020 was synthesized through the acylation of [11C]nicotinic acid, produced by the reaction of 3-bromopyrid...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-04-01
|
| Series: | EJNMMI Radiopharmacy and Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41181-025-00338-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849733035855970304 |
|---|---|
| author | Kazunori Kawamura Katsushi Kumata Tomoteru Yamasaki Masanao Ogawa Yusuke Kurihara Nobuki Nengaki Yukimi Nakamura Maiko Ono Yuhei Takado Hironaka Igarashi Ming-Rong Zhang |
| author_facet | Kazunori Kawamura Katsushi Kumata Tomoteru Yamasaki Masanao Ogawa Yusuke Kurihara Nobuki Nengaki Yukimi Nakamura Maiko Ono Yuhei Takado Hironaka Igarashi Ming-Rong Zhang |
| author_sort | Kazunori Kawamura |
| collection | DOAJ |
| description | Abstract Background [11C]TGN-020 has been developed as a positron emission tomography (PET) tracer for imaging aquaporin-4 (AQP4) in the brain and used in clinical studies. Previously, [11C]TGN-020 was synthesized through the acylation of [11C]nicotinic acid, produced by the reaction of 3-bromopyridine and n-butyllithium with [11C]CO2, with 2-amino-1,3,4-thiadiazole. In this study, to enhance the automated radiosynthesis efficiency of [11C]TGN-020, we optimized its radiosynthesis procedure using our in-house developed 11C-labeling synthesizer. Results [11C]TGN-020 was synthesized via direct [11C]CO2 fixation using n-butyllithium and 3-bromopyridine in tetrahydrofuran, followed by treatment of lithium [11C]nicotinic acetate with isobutyl chloroformate and subsequent acylation with 2-amino-1,3,4-thiadiazole in the presence of N,N-diisopropylethylamine. The optimized process significantly improved the radiosynthesis efficiency of [11C]TGN-020, achieving a high radiochemical yield based on [11C]CO2 (610‒1700 MBq, 2.8 ± 0.7%) at the end of synthesis (n = 12) and molar activity (A m) of 160–360 GBq/μmol at the end of synthesis (n = 5). The radiosynthesis time and radiochemical purity were approximately 60 min and > 95% (n = 12), respectively. PET studies based on [11C]TGN-020 with different A m values were performed using healthy rats. The radioactive uptake of [11C]TGN-020 with high A m in the cerebral cortex was slightly higher than that with low A m. Conclusions [11C]TGN-020 with high A m was obtained in reproducible radiochemical yield. Overall, the proposed optimization process for the radiosynthesis of [11C]TGN-020 can facilitate its application as a PET radiopharmaceutical for clinical use. |
| format | Article |
| id | doaj-art-2249b9e7c8e94d83a54a4be7a983170b |
| institution | DOAJ |
| issn | 2365-421X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-2249b9e7c8e94d83a54a4be7a983170b2025-08-20T03:08:09ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-04-0110111010.1186/s41181-025-00338-7Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020Kazunori Kawamura0Katsushi Kumata1Tomoteru Yamasaki2Masanao Ogawa3Yusuke Kurihara4Nobuki Nengaki5Yukimi Nakamura6Maiko Ono7Yuhei Takado8Hironaka Igarashi9Ming-Rong Zhang10Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Center for Integrated Human Brain Science, Brain Research Institute, Niigata UniversityQuantum Life Spin Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology (QST)Quantum Life Spin Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology (QST)Center for Integrated Human Brain Science, Brain Research Institute, Niigata UniversityDepartment of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST)Abstract Background [11C]TGN-020 has been developed as a positron emission tomography (PET) tracer for imaging aquaporin-4 (AQP4) in the brain and used in clinical studies. Previously, [11C]TGN-020 was synthesized through the acylation of [11C]nicotinic acid, produced by the reaction of 3-bromopyridine and n-butyllithium with [11C]CO2, with 2-amino-1,3,4-thiadiazole. In this study, to enhance the automated radiosynthesis efficiency of [11C]TGN-020, we optimized its radiosynthesis procedure using our in-house developed 11C-labeling synthesizer. Results [11C]TGN-020 was synthesized via direct [11C]CO2 fixation using n-butyllithium and 3-bromopyridine in tetrahydrofuran, followed by treatment of lithium [11C]nicotinic acetate with isobutyl chloroformate and subsequent acylation with 2-amino-1,3,4-thiadiazole in the presence of N,N-diisopropylethylamine. The optimized process significantly improved the radiosynthesis efficiency of [11C]TGN-020, achieving a high radiochemical yield based on [11C]CO2 (610‒1700 MBq, 2.8 ± 0.7%) at the end of synthesis (n = 12) and molar activity (A m) of 160–360 GBq/μmol at the end of synthesis (n = 5). The radiosynthesis time and radiochemical purity were approximately 60 min and > 95% (n = 12), respectively. PET studies based on [11C]TGN-020 with different A m values were performed using healthy rats. The radioactive uptake of [11C]TGN-020 with high A m in the cerebral cortex was slightly higher than that with low A m. Conclusions [11C]TGN-020 with high A m was obtained in reproducible radiochemical yield. Overall, the proposed optimization process for the radiosynthesis of [11C]TGN-020 can facilitate its application as a PET radiopharmaceutical for clinical use.https://doi.org/10.1186/s41181-025-00338-7Carbon-11Radiosynthesis[11C]TGN-020Positron emission tomographyAquaporin-4 |
| spellingShingle | Kazunori Kawamura Katsushi Kumata Tomoteru Yamasaki Masanao Ogawa Yusuke Kurihara Nobuki Nengaki Yukimi Nakamura Maiko Ono Yuhei Takado Hironaka Igarashi Ming-Rong Zhang Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020 EJNMMI Radiopharmacy and Chemistry Carbon-11 Radiosynthesis [11C]TGN-020 Positron emission tomography Aquaporin-4 |
| title | Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020 |
| title_full | Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020 |
| title_fullStr | Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020 |
| title_full_unstemmed | Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020 |
| title_short | Efficient one-pot radiosynthesis of the 11C-labeled aquaporin-4 inhibitor TGN-020 |
| title_sort | efficient one pot radiosynthesis of the 11c labeled aquaporin 4 inhibitor tgn 020 |
| topic | Carbon-11 Radiosynthesis [11C]TGN-020 Positron emission tomography Aquaporin-4 |
| url | https://doi.org/10.1186/s41181-025-00338-7 |
| work_keys_str_mv | AT kazunorikawamura efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT katsushikumata efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT tomoteruyamasaki efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT masanaoogawa efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT yusukekurihara efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT nobukinengaki efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT yukiminakamura efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT maikoono efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT yuheitakado efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT hironakaigarashi efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 AT mingrongzhang efficientonepotradiosynthesisofthe11clabeledaquaporin4inhibitortgn020 |