Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Nat Commun. 2024 Jul 15;15(1):5741. doi: 10.1038/s41467-024-50017-5.
Targeted alpha therapy (TAT) pairs the specificity of antigen targeting with the lethality of alpha particles to eradicate cancerous cells. Actinium-225 [Ac; t = 9.920(3) days] is an alpha-emitting radioisotope driving the next generation of TAT radiopharmaceuticals. Despite promising clinical results, a fundamental understanding of Ac coordination chemistry lags behind the rest of the Periodic Table due to its limited availability, lack of stable isotopes, and inadequate systems poised to probe the chemical behavior of this radionuclide. In this work, we demonstrate a platform that combines an 8-coordinate synthetic ligand and a mammalian protein to characterize the solution and solid-state behavior of the longest-lived Ac isotope, Ac [t = 21.772(3) years]. We expect these results to direct renewed efforts for Ac-TAT development, aid in understanding Ac coordination behavior relative to other +3 lanthanides and actinides, and more broadly inform this element's position on the Periodic Table.
靶向 α 治疗（TAT）将抗原靶向的特异性与 α 粒子的致命性结合起来，以消灭癌细胞。锕-225 [Ac；t=9.920(3)天]是一种发射α粒子的放射性同位素，推动了下一代 TAT 放射性药物的发展。尽管有 promising 的临床结果，但由于其有限的可用性、缺乏稳定同位素以及缺乏能够探测这种放射性核素化学行为的合适系统，Ac 的配位化学基础理解落后于元素周期表的其他部分。在这项工作中，我们展示了一个平台，该平台结合了一个 8 配位的合成配体和一种哺乳动物蛋白，以表征最长寿命的 Ac 同位素 Ac [t=21.772(3)年]在溶液和固态中的行为。我们期望这些结果能够指导 Ac-TAT 开发的重新努力，有助于了解 Ac 相对于其他 +3 镧系元素和锕系元素的配位行为，并更广泛地了解该元素在元素周期表中的位置。
