Next-generation Radioisotope Production with Inverse Kinematics Fusion Evaporation Reaction: On-line Isotope Separation for Targeted Alpha-therapy

Abstract Targeted alpha therapy using alpha-emitting radionuclides, such as ²¹¹At, is a promising treatment for certain cancers. However, its broader applications are hindered by production challenges: ²¹¹At must be chemically separated from the ²⁰⁹Bi target under high radiation, and beam energy constraints to avoid generating toxic long-lived contaminants ²¹⁰At reduce the production efficiency of ²¹¹At to one-fourth. Here, we show a novel inverse kinematics fusion evaporation method, where a heavy ²⁰⁹Bi beam irradiates a lighter ⁴He gas target — the “inverse” of beam and target nuclei relative to current normal kinematics method. This method produces ²¹¹At with higher forward velocity and narrower angular spread compared with those from the normal kinematics method, enabling physical isotope separation without chemical separation. On-line magnetic rigidity analysis further separates ²¹¹At from contaminants such as ²¹⁰At. The method also applies to isotopes such as ²²⁵Ac, whose production is often complicated by toxic long-lived isotopes. Radionuclides are rapidly collected via a gas transport system, allowing immediate use of radionuclides after irradiation. This approach achieves at least an order-of-magnitude higher production efficiency and enables clinical use of short-lived isotopes that are previously inaccessible due to time constraints.