Actinium-225 targeted alpha particle therapy for prostate cancer

Abstract

Targeted alpha particle therapy (TAT) has emerged as a promising strategy for the treatment of prostate cancer (PCa). Actinium-225 (²²⁵Ac), 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 ²²⁵Ac in PCa are PSMA-targeted TAT agents, notably [²²⁵Ac]Ac-PSMA-617, [²²⁵Ac]Ac-PSMA-I&T and [²²⁵Ac]Ac-J591. Ongoing investigations spotlight [²²⁵Ac]Ac-hu11B6, [²²⁵Ac]Ac-YS5, and [²²⁵Ac]Ac-SibuDAB, targeting hK2, CD46, and PSMA, respectively. Despite these efforts, hurdles in ²²⁵Ac 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 ²²⁷Th, ²²³Ra, ²¹¹At, ²¹³Bi, ²¹²Pb or ¹⁴⁹Tb, providing viable alternatives for TAT.

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