Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Dalton Trans. 2022 Mar 29;51(13):5041-5052. doi: 10.1039/d2dt00209d.
In recent years, copper-64 and copper-67 have been considered as a useful theranostic pair in nuclear medicine, due to their favourable and complementary decay properties. As Cu and Cu are chemically identical, development of both existing and new bifunctional chelators for Cu imaging agents can be readily adapted for the Cu-radionuclide. In this study, we explored the use of photoactivatable copper chelators based on the asymmetric bis(thiosemicarbazone) scaffold, HATSM/en, for the photoradiolabelling of protein. Photoactivatable CuATSM-derivatives were prepared by both direct synthesis and transmetallation from the corresponding Zn complex. Then, irradiation with UV light in the presence of a protein of interest in a pH buffered aqueous solution afforded the Cu-labelled protein conjugates in decay-corrected radiochemical yield of 86.9 ± 1.0% the transmetallation method and 35.3 ± 1.7% from the direct radiolabelling method. This study successfully demonstrates the viability of photochemically induced conjugation methods for the development of copper-based radiotracers for potential applications in diagnostic positron emission tomography (PET) imaging and targeted radionuclide therapy.
近年来，铜-64 和铜-67 因其良好的互补衰变特性，被认为是核医学中一种有用的治疗诊断对。由于 Cu 和 Cu 在化学上是相同的，因此现有的和新的双功能螯合剂都可以用于开发 Cu 成像剂，也可以很容易地适应 Cu-放射性核素。在这项研究中，我们探索了基于不对称双（硫代缩氨基脲）支架的光活化铜螯合剂 HATSM/en 在蛋白质光放射标记中的应用。通过直接合成和从相应的 Zn 配合物进行转金属化两种方法制备了光活化 CuATSM 衍生物。然后，在 pH 缓冲的水溶液中存在感兴趣的蛋白质时，用紫外线照射，通过转金属化方法获得了放射性化学收率为 86.9±1.0%的 Cu 标记蛋白缀合物，通过直接放射性标记方法获得了 35.3±1.7%的 Cu 标记蛋白缀合物。这项研究成功地证明了光化学诱导偶联方法在开发铜基放射性示踪剂方面的可行性，这些示踪剂可能应用于诊断正电子发射断层扫描（PET）成像和靶向放射性核素治疗。
