Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide

被引：82

作者：

Berndt, Mathias ^{[1
]}

Pietzsch, Jens ^{[1
]}

Wuest, Frank ^{[1
]}

机构：

[1] Res Ctr Rossendorf, Inst Radiopharm, D-01314 Dresden, Germany

来源：

NUCLEAR MEDICINE AND BIOLOGY | 2007年 / 34卷 / 01期

关键词：

positron emission tomography; F-18-labeled prosthetic group; LDL; lipoprotein modification; HUMAN APOLIPOPROTEIN-E; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; N-SUCCINIMIDYL; BINDING DOMAIN; GENERAL-METHOD; F-18; PROTEINS; OLIGONUCLEOTIDES; RECEPTOR;

D O I：

10.1016/j.nucmedbio.2006.09.009

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

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.

引用

页码：5 / 15

页数：11

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