Cancer is the second cause of death and morbidity in Europe. Unfortunately, currently available treatments cannot permanently cure most cancers, especially when metastatic. New therapy approaches are, therefore, urgently needed. Radionuclide therapy deposits cytotoxic radiation by means of energetic particles (alfa, beta, and auger) labeled to a carrier that specifically targets cancer cells. Targeted Alpha Therapy is very promising, because alpha particles deliver high energy (i.e., cytotoxic effect) in a small range, binding a target cell population without significant harm to healthy tissues. The high linear energy transfer typical of alpha particles determines irreversible double-strand DNA breaks with per-unit absorbed doses of acute biologic effects three-to-seven times greater than the damage produced by external beam with photons or beta radiation. As consequence, cells—not equipped to efficiently repair this type of damage—typically undergo death. Therefore, Targeted Alpha Therapy is such a new approach to treat tumors. This article aimed to provide an overview (five “W”s and “How”) on Targeted Alpha Therapy.

Graphical Abstract

中文翻译：

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定向阿尔法疗法的五个“ W”和“如何”：为什么？WHO？什么？哪里？什么时候？如何？

在欧洲，癌症是导致死亡和发病的第二大原因。不幸的是，当前可用的疗法无法永久治愈大多数癌症，尤其是在转移性癌症时。因此，迫切需要新的治疗方法。放射性核素疗法通过标记为特定靶向癌细胞的载体的高能粒子（阿尔法，β和螺旋钻）沉积细胞毒性放射。靶向Alpha疗法非常有前途，因为α粒子在很小的范围内提供了高能量（即细胞毒性作用），结合了靶细胞群而对健康组织没有明显伤害。典型的α粒子的高线性能量转移决定了不可逆的双链DNA断裂，其单位吸收剂量的急性生物效应比光子或β射线对外部光束产生的损害大三到七倍。结果，未配备有效修复此类损伤的细胞通常会死亡。因此，靶向阿尔法疗法是一种治疗肿瘤的新方法。本文旨在提供针对性Alpha疗法的概述（五个“ W”和“如何”）。

图形概要