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Improved synthesis of 6-bromo-7-[11C]methylpurine for clinical use
https://repo.qst.go.jp/records/2001013
https://repo.qst.go.jp/records/200101385c4db71-6c0c-4461-9ba5-4634f25d76ae
| アイテムタイプ | 学術雑誌論文 / Journal Article(1) | |||||||||||||
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| 公開日 | 2024-02-29 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Improved synthesis of 6-bromo-7-[11C]methylpurine for clinical use | |||||||||||||
| 言語 | en | |||||||||||||
| 言語 | ||||||||||||||
| 言語 | eng | |||||||||||||
| 資源タイプ | ||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||
| 資源タイプ | journal article | |||||||||||||
| 著者 |
Okamura Toshimitsu
× Okamura Toshimitsu
× Kikuchi Tatsuya
× Ogawa Masanao
× Zhang Ming-Rong
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | ABSTRACT Background: Multidrug resistance-associated protein 1 (MRP1), an energy-dependent efflux pump, is expressed widely in various tissues and contributes to many physiological and pathophysiological processes. 6-Bromo-7-[11C]methylpurine ([11C]7m6BP) is expected to be useful for the assessment of MRP1 activity in the human brain and lungs. However, the radiochemical yield (RCY) in the synthesis of [11C]7m6BP was low, limiting its clinical application, because the methylation of the precursor with [11C]CH3I provided primarily the undesired isomer, 6-bromo-9-[11C]methylpurine ([11C]9m6BP). To increase the RCY of [11C]7m6BP, we investigated conditions for improving the [11C]7m6BP/[11C]9m6BP selectivity of the methylation reaction. Results: [11C]7m6BP was manually synthesized via the methylation of 6-bromopurine with [11C]CH3I in various solvents and at different temperatures in the presence of potassium carbonate for 5 min. Several less polar solvents, including tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), and ethyl acetate (AcOEt) improved the [11C]7m6BP/[11C]9m6BP selectivity from 1:1 to 2:1, compared with the conventionally used solvents for the alkylation of 6-halopurines, acetone, acetonitrile, and N,N-dimethylformamide. However, a higher temperature (140°C or 180°C) was needed to progress the 11C-methylation in the less polar solvents, and the manual conditions could not be directly translated to an automated synthesis. [11C]Methyl triflate ([11C]CH3OTf) was thus used as a methylating agent to increase the conversion at a lower temperature. The 11C-methylation using [11C]CH3OTf at 100°C proceeded efficiently in THF, 2-MeTHF, and AcOEt with maintenance of the improved selectivity. Starting from 28 to 34 GBq [11C]CO2, [11C]7m6BP was produced with 2.3?2.6 GBq for THF, 2.7?3.3 GBq for AcOEt, and 2.8?3.9 GBq for 2-MeTHF at approximately 30 min after the end of bombardment (n = 3 per solvent). The isolated RCYs (decay corrected) for THF, 2-MeTHF, and AcOEt were 24%?28%, 29%?35%, and 22%?31% (n = 3), respectively. Conclusions: The use of THF, 2-MeTHF, and AcOEt improved the [11C]7m6BP/[11C]9m6BP selectivity in the methylation reaction, and the improved method provided [11C]7m6BP with sufficient radioactivity for clinical use. |
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| 書誌情報 |
EJNMMI Radiopharmacy and Chemistry 発行日 2024-02 |
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| 出版者 | ||||||||||||||
| 出版者 | Springer Nature | |||||||||||||
| ISSN | ||||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||||
| 収録物識別子 | 2365-421X | |||||||||||||
| DOI | ||||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | 10.1186/s41181-024-00240-8 | |||||||||||||
