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.

已经通过用[^ 18 F]亲核置换环状硫酸酯开发了6-脱氧-6-[^ 18 F]氟-L-抗坏血酸(^ 18 F-DFA)的一锅合成。 F]-氟离子，放射化学产率为 15%。在大鼠中用18 F-DFA进行的组织分布研究表明，在已知具有高浓度L-抗坏血酸的肾上腺、肾脏和肝脏器官中放射性的高摄取。静脉注射后 10 至 120 分钟之间观察到大脑中活动的缓慢和低摄取。注射。 18 F-DFA在携带3-甲基胆蒽诱导的纤维肉瘤的小鼠中和在脑中携带移植的RG-C6肿瘤的大鼠中的体内行为证明了其在肿瘤中积累的能力。正常大鼠和抗坏血酸缺乏的ODS大鼠中^ 18 F-DFA的组织积累的比较表明，大鼠内源性抗坏血酸不影响^ 18 F-DFA的体内行为。^<的脑区域分布18>F-DFA通过使用脑缺血的体内模型进行研究。通过切割椎动脉，然后用微血管夹闭塞颈动脉 20 分钟，诱导大鼠全身缺血。在缺血期结束后5天，观察到注射18 F-DFA后大脑皮层、下丘脑和杏仁核中放射性的摄取增加。这一发现提示^ 18 F-DFA可能在脑缺血后神经损伤的修复机制中发挥重要作用。因此，基于L-抗坏血酸用于正电子发射断层扫描的生化功能， 18 F-DFA似乎具有作为脑放射性药物的巨大潜力。

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。