The five “W”s and “How” of Targeted Alpha Therapy: Why? Who? What? Where? When? and How?

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.