A reverse ²³⁰U/²²⁶Th radionuclide generator for targeted alpha therapy applications

Purpose: Thorium-226 (half-life 30.6 m) is a radionuclide of interest for use in targeted alpha therapy applications. Due to its short half-life, ²²⁶Th must be provided through a radionuclide generator system from its parent ²³⁰U (20.8 d). Furthermore, as the half-life of ²²⁶Th is very short, it should be provided in a form that is directly amenable to use in biomedical applications. Methods: A reverse radionuclide generator system was developed employing a DGA extraction chromatography column. A ²³⁰U/²²⁶Th parent/daughter solution in equilibrium is added to a DGA column in >6 M HCl. The parent ²³⁰U is eluted first in 0.1 M HNO₃ followed by elution of ²²⁶Th in 0.1 M citrate buffer pH 5. Results: Thorium-226 was recovered from the radionuclide generator column with >96% yield. Greater than 99.5% of the ²³⁰U parent was isolated for reuse in the generator. Long term evaluation over six weeks demonstrated consistent supply of ²²⁶Th with greater than 99.5% radionuclidic purity. The only contaminant found in the final product was ²³⁰U (<0.5%). Conclusions: The reverse radionuclide generator described herein was shown to be a feasible method for providing ²²⁶Th in high yield, purity and in a chemical form that is amenable for direct use in biomedical applications.