| Japanese |
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| Title | [11C]McN5652X注射液の改良自動合成とマウス, ヒトにおける体内動態 |
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| Subtitle | 原著 |
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| Authors | 佐々木正大*,**, 須原哲也*, 久保寺昭子**, 鈴木和年* |
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| Organization | *放射線医学総合研究所高度診断機能研究ステーション, **東京理科大学薬学部 |
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| Journal | 核医学 |
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| Volume | 33 |
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| Number | 12 |
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| Page | 1319-1327 |
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| Year/Month | 1996/12 |
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| Article | 原著 |
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| Publisher | 日本核医学会 |
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| Abstract | 「要旨」 セロトニン再取り込み阻害剤である[11C]McN5652X{(6S,10bR)-trans-(+)-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline}はこれまで報告された他のセロトニントランスポーター標識リガンドに比較し, in vivoでの標的組織への集積が迅速であり, 特異結合の割合が高いことが報告されている. この化合物はSuehiroらにより反応基質{(6S,10bR)-trans-(+)-1,2,3,5,6,10b-hexahydro-6-[4-(mercapto)phenyl]pyrrolo-[2,1-a]-isoquinoline:A}を[11C]ヨウ化メチルでS-メチル化することによりはじめて合成された. しかし, Aは非常に反応性に富み分解しやすいため, その改良合成法が望まれていた. そこで, SH基保護剤であるDTT(Dithiothreitol)を添加することによりAを安定化し, かつ自動合成法を確立することにより比放射能181.3±7.4GBq/μmol, 放射化学的純度98.6±0.4%の[11c]McN5652x注射液を2.76±1.23GBqで得ることに成功した. この[11c]McN5652xをマウスに静注し, 安全性, 被ばく線量などについて前臨床評価を行った. マウスにおける脳内分布については, 視床, 線条体, 大脳皮質に高い集積が認められ, 健常人を対象としたPET計測では, 視床, 線条体, 中脳に高い集積が認められた. これまでのin vitroおよびin vivoのセロトニントランスポーターの分布の報告と同様の結果が確認された. |
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| Practice | 臨床医学：一般 |
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| Keywords | McN5652X, Serotonin transporter, PET, [11C] radioligands |
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| English |
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| Title | An Improved Automated Synthesis and In Vivo Evaluation of PET Radioligand for Serotonin Re-uptake Sites: [11C]McN5652X |
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| Subtitle | Original Articles |
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| Authors | Masahiro SASAKI*,**, Tetsuya SUHARA*, Akiko KUBODERA**, Kazutoshi SUZUKI* |
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| Authors(kana) | |
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| Organization | *Nationl Institutes of Radiological Science, **Faculy of Pharmaceuical Science, Science University of Tokyo |
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| Journal | The Japanese Journal of nuclear medicine |
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| Volume | 33 |
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| Number | 12 |
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| Page | 1319-1327 |
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| Year/Month | 1996/12 |
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| Article | Original article |
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| Publisher | THE JAPANESE SOCIETY OF NUCLEAR MEDICINE |
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| Abstract | [Summary] Carbon-11 labeled serotonin (5-HT) re-uptake inhibitor, [11C]McN5652X {(6S,10bR)-trans-(+)-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl] pyrrolo-[2,1-a]-isoquinoline}, has recently been reported to be favorable for studying human 5-HT re-uptake site by positron emission tomography (PET) because of its rapid and high specific binding characteristics as radioligands. [11C]McN5652X has been synthesized by S-methylation of the corresponding des-methyl precursor A with [11Cliodomethane. One serious disadvantage of this procedure, however, is the lack of stability of A. The improved method for the synthesis of A has been desired. We have found that the decomposition of A is significantly reduced by adding a protecting agent for SH groups, dithiothreitol (DTT), into the reaction medium immediately after the demethylation of McN5652X. By using this stabilized precursor A, we have developed an automated procedure giving [11C]McN5652X with 98.6+-0.4% radiochemical purity in high specific activity (181.3+-7.4 GBq/μmol). Preclinical evaluation of the product was carried out by injecting the solution of [11C]-McN5652X obtained by this procedure into mice. [11C]McN5652X showed the high accumulation into mouse thalamus, striatum and cerebral cortex, organs known to have high level of 5-HT receptor density, after intravenous injection. Human PET studies also showed the high uptakes of this radioligand into the thalamus, striatum and midbrain. |
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| Practice | Clinical medicine |
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| Keywords | McN5652X, Serotonin transporter, PET, [11C] radioligands |
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