One Step Radiosynthesis of 6-[18F]Fluoronicotinic Acid 2,3,5,6-Tetrafluorophenyl Ester ([18F]F-Py-TFP): A New Prosthetic Group for Efficient Labeling of Biomolecules with Fluorine-18
One Step Radiosynthesis of 6-[18F]Fluoronicotinic Acid 2,3,5,6-Tetrafluorophenyl Ester ([18F]F-Py-TFP): A New Prosthetic Group for Efficient Labeling of Biomolecules with Fluorine-18
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DOI：
10.1021/jm9015813
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发表时间：
2010-02-25
影响因子：
7.3
通讯作者：
Cuthbertson, Alan
中科院分区：
文献类型：
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作者：
Olberg, Dag E.;Arukwe, Joseph M.;Cuthbertson, Alan
用于正电子发射断层扫描(PET)的生物分子的标记几乎完全是在两步程序中使用假体基团完成的。该过程固有的复杂性使完全自动化成为一项挑战，并导致合成时间延长。在这里，我们描述了一个新的F-18标记的基于烟酸四氟苯酯的假体基团。在40℃下，[F-18]氟化物与三甲基铵前驱体反应，直接合成了6-[F-18]氟烟酸四氟苯酯([F-18]F-Py-TFP)，产率为60-70%。[F-18]F-Py-TFP在与含有RGD序列的多肽孵育之前，可通过Sep-Pak小柱方便地纯化。所需的偶联物形成速度快，产率高。建立了整合素α(V)β(3)的体外受体结合分析方法，以探讨与F-Py-TFP与I-125-ecstaatin制备的多肽和模拟多肽的竞争。研究发现，非放射性偶合物具有很高的结合亲和力，计算的K-I值在低纳摩尔范围内。
The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using prosthetic groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new F-18-labeled prosthetic group based on nicotinic acid tetrafluorophenyl ester. Reaction of [F-18]fluoride at 40 degrees C with the trimethylammonium precursor afforded 6-[F-18]fluoronicotinic acid tetrafluorophenyl ester ([F-18]F-Py-TFP) directly in 60-70% yield. [F-18]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin alpha(v)beta(3) was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with I-125-echistatin. The nonradioactive conjugates were found to possess high binding affinities with calculated K-i values in the low nanomolar range.