Purification of Actinium-225 from Thorium via Selective Precipitation

Numerous promising cancer treatments currently in clinical trials rely on the production and purification of actinium-225 (²²⁵Ac), an actinide with alpha emissions that can kill cancer cells via targeted alpha therapy. To enable ongoing and future studies, and to support anticipated future demand, it is necessary to increase the supply of ²²⁵Ac. High-energy proton irradiation of thorium metal (Th⁰_(s)) is one of the leading production methods of ²²⁵Ac. This process requires the chemical separation of microscopic amounts (μg) of ²²⁵Ac from large quantities (>10 g) of thorium. Current methods to accomplish this thorium removal step can be slow, tedious, generate large quantities of radioactive liquid waste, and require very strict control of the processing conditions. To improve this separation, we investigated the ability of four nitrate salts (NH₄NO₃, KNO₃, RbNO₃, and CsNO₃) to act as selective Th⁴⁺_(aq) precipitation agents in the presence of ²²⁵Ac³⁺_(aq) in aqueous nitric acid to allow for their separation through a simple filtration. First, we used an automated separations platform to screen the ability of these nitrate salts to precipitate Th⁴⁺. We found the Th⁴⁺ precipitation yields and amount of precipitating agent needed to maximize this yield were dependent on the identity of the precipitating agent cation. Separation studies with ²²⁵Ac³⁺_(aq) and subsequent down-selection of the most promising Th⁴⁺ precipitating agents and conditions enabled us to develop its effective selective precipitation. We demonstrated that the separation was compatible with Th⁰_(s) quantities that can produce medically relevant amounts of ²²⁵Ac. We observed 99.9% of Th⁴⁺_(aq) could be removed via precipitation with KNO_3(s) in less than two hours in the presence of co-produced isotopes. Meanwhile, other experiments demonstrated that the ²²⁵Ac³⁺_(aq) recovery was > 97% at 1-10 g Th⁰_(s) scale.