Preparation of an Actinium-228 Generator

Advances in targeted α-therapies have increased the interest in actinium (Ac), whose chemistry is poorly defined due to scarcity and radiological hazards. Challenges associated with characterizing Ac³⁺ chemistry are magnified by its 5f⁰6d⁰ electronic configuration, which precludes the use of many spectroscopic methods amenable to small amounts of material and low concentrations (like EPR, UV-vis, fluorescence). In terms of nuclear spectroscopy, many actinium isotopes (²²⁵Ac and ²²⁷Ac) are equally "unfriendly" because the actinium α-, β-, and γ-emissions are difficult to resolve from the actinium daughters. To address these issues, we developed a method for isolating an actinium isotope (²²⁸Ac) whose nuclear properties are well-suited for γ-spectroscopy. This four-step procedure isolates ²²⁸Ra from naturally occurring ²³²Th. The relatively long-lived ²²⁸Ra (t_1/2 = 5.75(3) years) radioisotope subsequently decays to ²²⁸Ac. Because the ²²⁸Ac decay rate [t_1/2 = 6.15(2) h] is fast, ²²⁸Ac rapidly regenerates after being harvested from the ²²⁸Ra parent. The resulting ²²⁸Ac generator provides frequent and long-term access (of many years) to the spectroscopically "friendly" ²²⁸Ac radionuclide. We have demonstrated that the ²²⁸Ac product can be routinely "milked" from this generator on a daily basis, in chemically pure form, with high specific activity and in excellent yield (∼95%). Hence, in the same way that developing synthesis routes to new starting materials has advanced coordination chemistry for many metals by broadening access, this ²²⁸Ac generator has the potential to broaden actinium access for the inorganic community, facilitating the characterization of actinium chemical behavior.