Department of Radiology and Biomedical Imaging, University of California San Francisco, CA-94107, USA.
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA-94107, USA.
Theranostics. 2024 May 11;14(7):2969-2992. doi: 10.7150/thno.96403. eCollection 2024.
Targeted alpha particle therapy (TAT) has emerged as a promising strategy for the treatment of prostate cancer (PCa). Actinium-225 (Ac), a potent alpha-emitting radionuclide, may be incorporated into targeting vectors, causing robust and in some cases sustained antitumor responses. The development of radiolabeling techniques involving EDTA, DOTA, DOTPA, and Macropa chelators has laid the groundwork for advancements in this field. At the forefront of clinical trials with Ac in PCa are PSMA-targeted TAT agents, notably [Ac]Ac-PSMA-617, [Ac]Ac-PSMA-I&T and [Ac]Ac-J591. Ongoing investigations spotlight [Ac]Ac-hu11B6, [Ac]Ac-YS5, and [Ac]Ac-SibuDAB, targeting hK2, CD46, and PSMA, respectively. Despite these efforts, hurdles in Ac production, daughter redistribution, and a lack of suitable imaging techniques hinder the development of TAT. To address these challenges and additional advantages, researchers are exploring alpha-emitting isotopes including Th, Ra, At, Bi, Pb or Tb, providing viable alternatives for TAT.
靶向 α 粒子治疗（TAT）已成为治疗前列腺癌（PCa）的一种有前途的策略。锕-225（Ac）是一种强效的 α 发射放射性核素，可被掺入靶向载体中，导致强烈且在某些情况下持续的抗肿瘤反应。涉及 EDTA、DOTA、DOTPA 和 Macropa 螯合剂的放射性标记技术的发展为该领域的进展奠定了基础。在 PSMA 靶向 TAT 药物的临床试验中处于前沿的是 Ac，特别是 [Ac]Ac-PSMA-617、[Ac]Ac-PSMA-I&T 和 [Ac]Ac-J591。正在进行的研究强调了针对 hK2、CD46 和 PSMA 的 [Ac]Ac-hu11B6、[Ac]Ac-YS5 和 [Ac]Ac-SibuDAB。尽管有这些努力，但 Ac 的生产、子体再分布以及缺乏合适的成像技术等障碍阻碍了 TAT 的发展。为了解决这些挑战和其他优势，研究人员正在探索包括 Th、Ra、At、Bi、Pb 或 Tb 在内的发射 α 粒子的同位素，为 TAT 提供了可行的替代方案。
