Positron emission tomography (PET) is a non-invasive molecular imaging technology that is constantly expanding, with a high demand for specific antibody-derived imaging probes. The use of tracers based on temperature-sensitive molecules (i. e. Fab, svFab, nanobodies) is increasing and has led us to design a class of chelators based on the structure of 2-aminomethylpiperidine (AMP) with acetic and/or hydroxybenzyl pendant arms (2-AMPTA, NHB-2-AMPDA, and 2-AMPDA-HB), which were investigated as such for {Al18 F}2+ -core chelation efficiency. All the compounds were characterized by HPLC-MS analysis and NMR spectroscopy. The AlF-18 labeling reactions were performed under various conditions (pH/temperature), and the radiolabeled chelates were purified and characterized by radio-TLC and radio-HPLC. The stability of labeled chelates was investigated up to 240 min in human serum (HS), EDTA 5 mM, PBS and 0.9 % NaCl solutions. The in vivo stability of [Al18 F(2-AMPDA-HB)]- was assessed in healthy nude mice (n=6). Radiochemical yields between 55 % and 81 % were obtained at pH 5 and room temperature. High stability in HS was measured for [Al18 F(2-AMPDA-HB)]- , with 90 % of F-18 complexed after 120 min. High stability in vivo, rapid hepatobiliary and renal excretion, with low accumulation of free F-18 in bones were measured. Thus, this new Al18 F-chelator may have a great impact on immuno-PET radiopharmacy, by facilitating the development of new fluorine-18-labeled heat-sensitive biomolecules.

中文翻译：

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用于PET成像的2-氨基甲基哌啶基螯合剂的室温Al18 F标记。

正电子发射断层扫描（PET）是一种不断发展的非侵入性分子成像技术，对特定的抗体衍生成像探针有很高的需求。基于对温度敏感的分子（例如Fab，svFab，纳米抗体）的示踪剂的使用正在增加，并导致我们基于带有乙酸和/或羟苄基侧链的2-氨基甲基哌啶（AMP）的结构设计一类螯合剂（ 2-AMPTA，NHB-2-AMPDA和2-AMPDA-HB）就{Al18 F} 2 +-核螯合效率进行了研究。通过HPLC-MS分析和NMR光谱对所有化合物进行表征。AlF-18标记反应是在各种条件（pH /温度）下进行的，放射性标记的螯合物经放射-TLC和放射-HPLC纯化和表征。在人血清（HS），5 mM EDTA，PBS和0.9％NaCl溶液中长达240分钟的时间内研究了标记的螯合物的稳定性。在健康的裸鼠（n ＝ 6）中评估了[Al18 F（2-AMPDA-HB）]-的体内稳定性。在pH 5和室温下，放射化学收率在55％至81％之间。对于[Al18 F（2-AMPDA-HB）]-，在HS中具有很高的稳定性，在120分钟后有90％的F-18络合。测量了体内的高稳定性，快速的肝胆和肾脏排泄以及游离F-18在骨骼中的积聚少。因此，通过促进新的氟18标记的热敏生物分子的开发，这种新的Al18 F螯合剂可能会对免疫PET放射药物产生重大影响。在pH 5和室温下，放射化学收率在55％至81％之间。对于[Al18 F（2-AMPDA-HB）]-，在HS中具有很高的稳定性，在120分钟后有90％的F-18络合。测量了体内的高稳定性，快速的肝胆和肾脏排泄，以及游离F-18在骨骼中的积聚少。因此，通过促进新的氟18标记的热敏生物分子的开发，这种新的Al18 F螯合剂可能会对免疫PET放射药物产生重大影响。在pH 5和室温下，放射化学收率在55％至81％之间。对于[Al18 F（2-AMPDA-HB）]-，在HS中具有很高的稳定性，在120分钟后有90％的F-18络合。测量了体内的高稳定性，快速的肝胆和肾脏排泄以及游离F-18在骨骼中的积聚少。因此，通过促进新的氟18标记的热敏生物分子的开发，这种新的Al18 F螯合剂可能会对免疫PET放射药物产生重大影响。