Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide
Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide
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DOI：
10.1016/j.nucmedbio.2006.09.009
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Wuest, Frank
中科院分区：
文献类型：
--
作者：
Berndt, Mathias;Pietzsch, Jens;Wuest, Frank
研制了新型硫醇选择性双功能F-18标记剂N-[6-(4-[F-18]fluoro-benzylidene)aminooxyhexyl]maleimide([F-18]FBAM)。以N-(6-氨基氧基己基)马来酰亚胺为原料，通过三步反应合成了N-(6-氨氧基己基)马来酰亚胺双官能团，总收率59%。随后用4-[F-18]氟苯甲醛放射性标记得到双功能F-18-标记剂[F-18]FBAM，放化产率为29%。在一个典型的实验中，3.88GBq的[F-18]氟化物可以在69分钟内转化为723MBq的[F-18]FBAM。[F-18]FBAM与硫醇基团的结合是以含有半胱氨酸的三肽谷胱甘肽和人低密度脂蛋白亚组分的各种载脂蛋白为例的。以人肝癌细胞(HepG2)对[F-18]FBAM-LDL消减的摄取为指标评价后者的作用。在大鼠体内的生物分布研究表明，[F-18]FBAM-LDL减去物具有很高的稳定性。此外，通过使用专用小动物断层摄影术进行的动态正电子发射断层扫描研究，描绘了[F-18]FBAM-LDL减除物在体内的代谢命运。数据与以前使用NH2反应性F-18-标记剂N-琥珀酰亚胺-4-[F-18]氟苯甲酸酯的研究进行了比较。化合物[F-18]FBAM可以被认为是一种很好的修复基，用于选择性和温和地标记含有硫醇的生物分子，适合于随后的体外和体内研究。(C)2007 Elsevier Inc.保留所有权利。
The novel thiol-group-selective bifunctional F-18-labeling agent N-[6-(4-[F-18]fluoro-benzylidene)aminooxyhexyl]maleimide ([F-18]FBAM) has been developed. The bifunctional labeling precursor N-(6-aminoxyhexyl)maleimide containing a thiol-reactive maleimide group and a carbonyl-group-reactive aminooxy group was prepared in only three steps in a total chemical yield of 59%. Subsequent radiolabeling with 4-[F-18]fluorobenzaldehyde gave the bifunctional F-18-labeling agent [F-18]FBAM in a radiochemical yield of 29%. In a typical experiment, 3.88 GBq of [F-18]fluoride could be converted into 723 MBq of [F-18]FBAM within 69 min. Conjugation of [F-18]FBAM with thiol groups was exemplified with the cystein-containing tripeptide glutathione and with various apolipoproteins of human low-density lipoprotein (LDL) subfractions. The latter was evaluated with respect to the uptake of [F-18]FBAM-LDL subtractions in human hepatoma cells (HepG2) in vitro. In vivo biodistribution studies in rats revealed high stability for [F-18]FBAM-LDL subtractions. Moreover, the metabolic fate of [F-18]FBAM-LDL subtractions in vivo was delineated by dynamic positron emission tomography studies using a dedicated small animal tomograph. Data were compared to former studies that used the NH2-reactive F-18-labeling agent N-succinimidyl-4-[F-18]fluorobenzoate. The compound [F-18]FBAM can be considered as an excellent prosthetic group for the selective and mild F-18 labeling of thiol-group-containing biomolecules suitable for subsequent investigations in vitro and in vivo. (c) 2007 Elsevier Inc. All rights reserved.