Scale up, scale down of a process for materials with no weighable mass….Who needs a scale?

Abstract: Actinium-225 (Ac-225) has emerged as an isotope that can be used in targeted radiotherapy to treat cancers. The field of targeted radiotherapy and radioisotope production presents unique challenges where commercial batches at Ci levels may have a mass of only µgrams or less but could be used to treat hundreds of patients. During radioisotope production cyclotrons, nuclear reactors or rhodotrons are used to irradiate 0.2-100 grams of target material to make a specific isotope. To increase yield and purity some targets may contain expensive enriched isotopes that need to be recycled, or larger target masses may be used. Scaling up the irradiation process is unique as target survivability can be a major challenge due to the build up of heat in the target leading to catastrophic failures. Different approaches will be discussed to limit target failures. Chemical purification can be difficult because several variables need to be evaluated. The processing time, yields, recycling enriched target materials, radiochemical and chemical purity all impact the process that is chosen. The US DOE Isotope program formed a Tri-Lab team, and they focused on producing commercial levels of Ac-225 from proton irradiation of Thorium-232 at their linear accelerators. The scale up of a separation step to remove ~90% of Thorium-232 at 10- and 100-grams quantities from <0.1 mgrams of Actinium-225 will be discussed. A process was developed for a 10-gram target and is currently being used for production of Ac-225. Prior to developing a scaled-up process to 100 grams eight separation approaches were evaluated based on: process time, the amounts of radioactive waste generated during the process, problems with solubility and column capacity, regulatory and safety issues. For a 100-gram thorium target a solvent extraction step was developed which was able to remove 95% of the thorium and recover 98.7% of Ac-225.