葡萄糖转运蛋白显像剂6-18FDG的制备及在小鼠体内的分布

高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (12): 2419.

葡萄糖转运蛋白显像剂6-18FDG的制备及在小鼠体内的分布

张政伟^1,2, 钱隽¹, 薛方平², 刘平², 李燕茹¹, 管一晖², 朱建华¹

1. 复旦大学药学院放射药学教研室, 上海 200232;
2. 复旦大学附属华山医院PET中心, 上海 200235

收稿日期:2009-02-23 出版日期:2009-12-10 发布日期:2009-12-10
通讯作者: 朱建华, 男, 教授, 博士生导师, 主要从事放射性药物研究. E-mail: jhzhu@shmu.edu.cn; 管一晖, 男, 主任医师, 主要从事核医学研究. E-mail: guanyihui@hotmail.com
基金资助:
国家“九七三”计划项目(批准号: 2007CB935800)资助.

One-pot Synthesis and Biodistribution of 6-[¹⁸F]Fluoro-6-deoxy-D-glucose(6-¹⁸FDG) as Potential Glucose Transport Imaging Agent

ZHANG Zheng-Wei^1,2, QIAN Jun¹, XUE Fang-Ping², LIU Ping², LI Yan-Ru¹, GUAN Yi-Hui^2*, ZHU Jian-Hua^1*

1. Department of Radiopharmacy, School of Pharmacy, Fudan University, Shanghai 200232, China;
2. PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China

Received:2009-02-23 Online:2009-12-10 Published:2009-12-10
Contact: ZHU Jian-Hua. E-mail: jhzhu@shmu.edu.cn; GUAN Yi-Hui. E-mail: guanyihui@hotmail.com
Supported by:
国家“九七三”计划项目(批准号: 2007CB935800)资助.

摘要/Abstract

摘要：

为了研究正电子核素¹⁸F标记的葡萄糖转运蛋白显像剂6-¹⁸氟-6-脱氧葡萄糖的制备及在小鼠体内的生物学分布, 以D-葡萄糖为起始原料, 经过丙酮和苯甲醛对1,2,3,5位羟基的定位保护, 然后用对甲苯磺酰氯和6位的羟基反应得到能被¹⁸F^-进攻的离去基团, 最后用¹⁸F^-离子通过亲核取代反应实现对葡萄糖6位的氟代标记; 反应中间体用NMR和MS表征, 最终产物用标准品6-¹⁹FDG在HPLC下对照确认, 测定放化纯度, 观察其在小鼠体内的生物学分布. 6-¹⁸氟-6-脱氧葡萄糖的放射性标记过程需35 min(从加速器轰击结束算起), 放化产率70%±5%(校正后, n=5), 放化纯度>95%. 小鼠体内的生物学分布表明, 各个器官在1.0 min达到峰值, 然后逐渐平衡. 初步研究结果表明, 6-¹⁸FDG是一种很有价值的葡萄糖转运蛋白显像剂, 为以后的体内外研究及活体显像奠定了基础.

关键词: 正电子发射计算机断层扫描; 葡萄糖转运蛋白; 6-18氟6-脱氧-D-葡萄糖; 一锅法合成

Abstract:

For the development glucose transport imaging, a radioactive glucose analogue was synthesized and evaluated. A glucose analogue, 6-[¹⁸F]fluoro-6-deoxy-D-glucose(6-¹⁸FDG), was prepared in two steps with one-pot synthesis from [¹⁸F]fluoride and tosyl-precursor. Starting with D-glucose, the D-glucose was reacted with acetone and benzaldehyde to protect hydoxy, then reacted with p-toluenesulfonyl choride(TsCl) to get the tosyl-precursor. All the intermediates were identified with NMR and MS. The total radiosysthesis spent 35 min and with 70%±5%(EOB, decay corrected, n=5), with the radiochemical purity>95%. Biodistribution of 6-¹⁸FDG was performed in mice: ¹⁸F activities in brain, liver, and heart reach the peak in 1.0 min after the injection, so reached a constant level. These results support that 6-¹⁸FDG is promising as valid tracer of glucose transport.

Key words: Positron emission tomography; Glucose transport; 6-[18F] Fluoro-6-deoxy-D-glucose; One-pot synthesis

TrendMD:

张政伟, 钱隽, 薛方平, 刘平, 李燕茹, 管一晖, 朱建华. 葡萄糖转运蛋白显像剂6-18FDG的制备及在小鼠体内的分布. 高等学校化学学报, 2009, 30(12): 2419.

ZHANG Zheng-Wei, QIAN Jun, XUE Fang-Ping, LIU Ping, LI Yan-Ru, GUAN Yi-Hui, .... One-pot Synthesis and Biodistribution of 6-[¹⁸F]Fluoro-6-deoxy-D-glucose(6-¹⁸FDG) as Potential Glucose Transport Imaging Agent. Chem. J. Chinese Universities, 2009, 30(12): 2419.

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