Univ Brest, UMR CNRS 6521 CEMCA, 6 avenue Victor le Gorgeu, 29238, Brest, France) E-mail: s.
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal.
Chemistry. 2022 Jul 20;28(41):e202200942. doi: 10.1002/chem.202200942. Epub 2022 Jun 10.
The limited use of palladium-103 and -109 radionuclides for molecular radiotherapy is surely due to the lack of appropriate ligands capable of fulfilling all criteria required for application in nuclear medicine. Furthermore, the thermodynamic properties of these complexes in solution remain difficult to establish. The challenge is compounded when considering that radiolabeling of compounds for translation to clinical trials requires fast complexation. Thus, the coordination of Pd(II) and Pd-nuclides is a huge challenge in terms of molecular design and physicochemical characterization. Herein, we report a comprehensive study highlighting TE1PA, a monopicolinate cyclam - already established in nuclear imaging with Cu-PET (positron emission tomography) imaging tracers - as a highly relevant chelator for natural Pd and subsequently Pd-nuclide. The structural, thermodynamic, kinetic and radiolabeling studies of Pd(II) with TE1PA, as well as the comparison of this complex with three structurally related derivatives, support palladium-TE1PA radiopharmaceuticals as leading candidates for targeted nuclear medicine.
钯-103 和 -109 放射性核素在分子放疗中的应用受到限制，这主要是由于缺乏能够满足核医学应用所有要求的合适配体。此外，这些配合物在溶液中的热力学性质仍然难以确定。当考虑到化合物的放射性标记需要快速络合以转化为临床试验时，挑战就更加复杂了。因此，Pd(II)和 Pd-核素的配位在分子设计和物理化学表征方面是一个巨大的挑战。本文报道了一项全面的研究，重点介绍了 TE1PA，这是一种已经在核成像中使用 Cu-PET（正电子发射断层扫描）成像示踪剂的单吡啶酸环烷，它是一种非常相关的天然 Pd 和随后的 Pd-核素螯合剂。对 Pd(II)与 TE1PA 的结构、热力学、动力学和放射性标记研究，以及与三种结构相关衍生物的比较，支持钯-TE1PA 放射性药物作为靶向核医学的候选药物。
