DEVELOPMENT OF RADIOPHARMACEUTICALS BASED ON THE BIOCHEMICAL FUNCTIONS OF ASCORBIC ACID

基于抗坏血酸生化功能的放射性药物的开发

• 批准号: 03453150
• 负责人: MAEDA Minoru
• 金额: $ 2.43万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03453150/
• 关键词: L-ascorbic acid; 6-deoxy-6-[^<18>F]fluoro-L-ascorbic acid; fluorine-18; tissue distribution; brain ischemia; radiopharmaceutical; 6-デオキシ-6-〔F-18〕フルオロ-L-アスコルビン酸; フッ素-18; 脳虚血ラット; Lーアスコルビン酸; フルオロアスコルビン酸; 腫瘍

A one-pot synthesis of 6-deoxy-6-[^<18>F]fluoro-L-ascorbic acid (^<18>F-DFA) has been developed via nucleophilic displacement of a cyclic sulfate with [^<18>F]- fluoride ion in 15% radiochemical yield. Tissue distribution studies with ^<18>F-DFA in rats showed high uptake of radioactivity in the adrenals, kidneys and liver-organs known to have high concentration of L-ascorbic acid. The slow and low uptake of activity in the brain was observed between 10 and 120 min after i.v. injection. In vivo behavior of ^<18>F-DFA in mice bearing 3- methylcholanthrene-induced fibrosarcoma, and in rats bearing transplanted RG-C6 tumor in brain demonstrated its ability to accumulate in the tumors. Comparison of tissue accumulation of ^<18>F-DFA in normal rats and ascorbic acid deficient ODS rats indicated that endogenous ascorbic acid in rats does not affect the in vivo behavior of ^<18>F-DFA.Regional brain distribution of ^<18>F-DFA was investigated by using in vivo model of cerebral ischemia. Global ischemia was induced in rats by cutting arteiae vertebralis, and then occluding carotid arteries with a microvascular clamp for 20 min. Increased uptake of radioactivity in the cerebral cortex, hypothalamus and amygdala followed by injection of ^<18>F-DFA was observed at 5 days after the termination of the ischemic period. This finding suggests that ^<18>F-DFA may play an important role in repair mechanism of neural injury after cerebral ischemia. Thus, ^<18>F-DFA seemingly has a great potential as a brain radiopharmaceutical based on the biochemical functions of L-ascorbic acid for positron emission tomography.

6-脱氧-6 - [^<18> f]氟-l-抗坏血酸（^<18> f-DFA）的一盘合成是通过含有[^<18> f] - 氟离子离子的15％放射药产量的氟化物离子的环硫酸盐的核位移来开发的。在大鼠中使用 ^<18> F-DFA的组织分布研究表明，已知具有高浓度的L-抗坏血酸的肾上腺，肾脏和肝脏中的放射性吸收。在静脉注射后10到120分钟之间观察到大脑中的缓慢和低吸收。注射。在带有3-甲基胆素诱导的纤维肉瘤的小鼠中 ^<18> f-DFA的体内行为，在脑中带有移植RG-C6肿瘤的大鼠中表明其在肿瘤中积聚的能力。在正常大鼠和抗坏血酸中的 ^<18> f-DFA的组织积累的比较表明，大鼠的内源性抗坏血酸不会影响 ^<18> f-dfa的体内行为。使用塞雷布尔伊斯米亚氏菌的体内模型，研究了 ^<18> f-dfa的体内 ^<18> f-dfa的 ^<18> f-dfa的区域分布。通过切割Arteiae椎骨，在大鼠中诱导全球缺血，然后用微血管夹具锁定颈动脉20分钟。在缺血时期终止5天后，观察到脑皮质，下丘脑和杏仁核的放射性吸收增加，然后注射 ^<18> F-DFA。这一发现表明， ^<18> F-DFA在脑缺血后神经损伤的修复机制中可能起重要作用。因此， ^<18> f-dfa似乎具有基于L-抗坏血酸的生化功能的脑部放射性功能的脑部放射性药物的巨大潜力，用于正电子发射断层扫描。

项目成果

山本 文彦,佐々木 茂貴,前田 稔: "Positron Labeled Analogs of Antioxidants:Synthesis and Tissue Biodistribution of 6ーDeoxyー6ー〔 ^<18>F〕fluoroーLーascorbic Acid" Appl.Radiat.Isotopes. 43. (1992)

Fumihiko Yamamoto、Shigetaka Sasaki、Minoru Maeda：“抗氧化剂的正电子标记类似物：6-脱氧-6-[^<18>F]氟-L-抗坏血酸的合成和组织生物分布”Appl.Radiat.Isotopes 43。 1992）

山本 文彦,佐々木 茂貴,前田 稔: "Positron Labeled Antioxidants:Synthesis and Tissue Biodistribution of 6-Deoxy-6-[ ^<18>F]fluoro-L-ascorbic Acid" Appl.Radiat.Isot.43. 633-639 (1992)

Fumihiko Yamamoto、Shigetaka Sasaki、Minoru Maeda：“正电子标记的抗氧化剂：6-脱氧-6-[ ^<18>F]氟-L-抗坏血酸的合成和组织生物分布”Appl.Radiat.Isot.43。 (1992)

山本 文彦,佐々木 茂貴,前田 稔: "Positron Labeled Antioxidants:Synthesis and Tissue Biodistribution of 6-Deoxy-6〔^<18>F〕fluoro-L-ascorbic Acid" Appl.Radiat.Isot.43. 633-639 (1992)

Fumihiko Yamamoto、Shigetaka Sasaki、Minoru Maeda：“正电子标记的抗氧化剂：6-Deoxy-6〔^<18>F〕氟-L-抗坏血酸的合成和组织生物分布”Appl.Radiat.Isot.43（ 1992）

R. YAMAMOTO, S. SASAKI and M. MAEDA: "Positron Labeled Antioxidants:Synthesis and Tissue Biodistribution of 6-deoxy-6-[F-18]fluoro-L-ascorbic acid" Appl. Radiat. Isot.Vol.43, No.5. 633-639 (1992)

R. YAMAMOTO、S. SASAKI 和 M. MAEDA：“正电子标记的抗氧化剂：6-脱氧-6-[F-18]氟-L-抗坏血酸的合成和组织生物分布”应用。