Synthesis and application of [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO):: A [18F]FDG-based prosthetic group for the chemoselective 18F-labeling of peptides and proteins
Synthesis and application of [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO):: A [18F]FDG-based prosthetic group for the chemoselective 18F-labeling of peptides and proteins
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DOI：
10.1021/bc8000112
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Pietzsch, Jens
中科院分区：
文献类型：
--
作者：
Wuest, Frank;Berndt, Mathias;Pietzsch, Jens
2-[F-18]氟-2-脱氧-D-葡萄糖（[F-18]FDG）作为最重要的PET放射性示踪剂，几乎每个PET中心都有提供。然而，使用[F-18]FDG作为用于合成18 F-标记化合物的结构单元的实例非常少。本研究描述了使用[F-18]FDG作为用于合成F-18标记的肽和蛋白质的构建块。[F-18]FDG被转化为[F-18] FDG-马来酰亚胺己基肟（[F-18]FDG-MHO），这是一种新型的基于[F-18] FDG的辅基，用于肽和蛋白质的温和和巯基特异性的F-18标记。反应在100 ° C下在含有[F-18]FDG和N-（6-氨氧基-己基）马来酰亚胺的80%乙醇中的密封通孔中进行15分钟。[v]在45 min的总合成时间内，经HPLC纯化后，以45-69%的放射化学产率（基于[F-18]FDG）获得FDG-MHO。通过与三肽谷胱甘肽（GSH）和含单半胱氨酸的蛋白膜联蛋白A5（anxA 5）反应，研究了F-18]FDG-MHO与巯基的化学选择性缀合。以43-58%的放射化学产率（基于[F-18] FDG-MHO，n = 6）获得放射性标记的膜联蛋白A5（[F-18] FDG-MHO-anxA 5），并将[F-18]FDG-MHO-anxA 5用于试验性小动物PET研究，以评估HT-29小鼠异种移植模型中的体内生物分布和动力学。
2-[F-18]Fluoro-2-deoxy-D-glucose ([F-18]FDG) as the most important PET radiotracer is available in almost every PET center. However, there are only very few examples using [F-18]FDG as a building block for the synthesis of 18 F-labeled compounds. The present study describes the use of [F-18]FDG as a building block for the synthesis of F-18-labeled peptides and proteins. [F-18]FDG was converted into [F-18]FDG-maleimidehexyloxime ([F-18]FDG-MHO), a novel [F-18]FDG-based prosthetic group for the mild and thiol group-specific F-18 labeling of peptides and proteins. The reaction was performed at 100 degrees C for 15 min in a sealed via] containing [F-18]FDG and N-(6-aminoxy-hexyl)maleimide in 80% ethanol. [v]FDG-MHO was obtained in 45-69% radiochemical yield (based upon [F-18]FDG) after HPLC purification in a total synthesis time of 45 min. Chemoselecetive conjugation of F-18]FDG-MHO to thiol groups was investigated by the reaction with the tripeptide glutathione (GSH) and the single cysteine containing protein annexin A5 (anxA5). Radiolabeled annexin A5 ([F-18]FDG-MHO-anxA5) was obtained in 43-58% radiochemical yield (based upon [F-18]FDG-MHO, n = 6), and [F-18]FDG-MHO-anxA5 was used for a pilot small animal PET study to assess in vivo biodistribution and kinetics in a HT-29 murine xenograft model.