Toms Johannes, Reshetnikov Viktor, Maschauer Simone, Mokhir Andriy, Prante Olaf
Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Department of Chemistry and Pharmacy, Organic Chemistry Chair II, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
J Labelled Comp Radiopharm. 2018 Dec;61(14):1081-1088. doi: 10.1002/jlcr.3687. Epub 2018 Oct 18.
The imaging of reactive oxygen species (ROS) at the molecular level with high sensitivity and specificity by positron emission tomography (PET) could be of enormous interest to increase our knowledge about ROS activity and signalling, especially in tumours. The aim of this research was to optimise the click chemistry-based radiosynthesis of an F-labelled aminoferrocene glycoconjugate that was derived from an N-alkylaminoferrocene lead structure known to have anticancer activity in vitro. Applying the solvent system phosphate buffer/THF (12/5), Cu(OAc) and sodium ascorbate as reducing agent at 60°C, the alkyne 1 reacted with the F-labelled glycosyl azide [ F]2 in the presence of carrier 3 (47μM) to obtain carrier-added [ F]4 in a radiochemical yield of 85%. Interestingly, the addition of carrier was essential for sufficient radiochemical yield, because it suppressed the oxidation of no-carrier-added (n.c.a.) [ F]4. Future work will include the formulation of c.a. [ F]4 for studying its biodistribution in tumour-bearing mice.
通过正电子发射断层扫描（PET）在分子水平上以高灵敏度和特异性对活性氧（ROS）进行成像，对于增进我们对ROS活性和信号传导的了解，尤其是在肿瘤方面，可能具有极大的意义。本研究的目的是优化基于点击化学的F标记氨基二茂铁糖缀合物的放射性合成，该缀合物源自已知在体外具有抗癌活性的N-烷基氨基二茂铁铅结构。在60°C下，使用磷酸盐缓冲液/四氢呋喃（12/5）溶剂体系、醋酸铜（Cu(OAc)）和抗坏血酸钠作为还原剂，炔烃1在载体3（47μM）存在下与F标记的糖基叠氮化物[F]2反应，以85%的放射化学产率获得添加载体的[F]4。有趣的是，添加载体对于获得足够的放射化学产率至关重要，因为它抑制了无载体添加（n.c.a.）的[F]4的氧化。未来的工作将包括配制添加载体的[F]4，以研究其在荷瘤小鼠中的生物分布。
