Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes

• Actinium-225 (t1/2 = 9.92 d) is an α-emitting radionuclide for use in targeted alpha therapy.
• During proton irradiation of thorium metal, long-lived 227Ac (t1/2 = 21.8 a) is co-produced.
• An efficient Ac/Th separation procedure is required for rapid 225Ac/227Ac ratio determination.
• For Ac isolation, a sequence of cation exchange and extraction chromatography was implemented.
• Ac is isolated from Th and then purified from fission lanthanides via extraction chromatography.

Actinium-225 (t1/2 = 9.92 d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for 213Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived 227Ac (t1/2 = 21.8 a, 99% β−, 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the 225Ac/227Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An 225Ac spike added prior to separation was recovered at ≥98%, and Ac decontamination from Th was found to be ≥106. The purified actinium fraction allowed for highly accurate 227Ac determination at analytical scales, i.e., at 227Ac activities of 1–100 kBq (27 nCi to 2.7 μCi).