Construction of a thorium/actinium generator at the Canadian Nuclear Laboratories

Targeted Alpha Therapy (TAT) has demonstrated considerable promise in the treatment of a range of cancers in both preclinical and, more recently clinical research. In particular, work with the alpha-emitting radionuclide Ac-225 has been effectively employed due to the relatively rapid decay cascade that leads to 4 alpha and 2 beta emissions. One limitation for TAT has been caused by access to the vital radionuclide. Traditionally, Ac-225 has been sourced from thorium/actinium generators based on the alpha decay of stockpiles of Th-229. Th-229 is itself the alpha-decay product from U-233. Due to proliferation issues associated with U-233, only three thorium/actinium generators have been reported in the literature, capable of supporting clinical research. This paper describes the construction and operation of a thorium/actinium radionuclide generator at the Canadian Nuclear Laboratories, capable of supporting preclinical and limited clinical research in the area of TAT. Thorium was recovered and purified by a combination of anion exchange and extraction chromatography from aged U-233 stockpiles. A separation scheme for Ra-225 and Ac-225 has been developed, based upon the chemical composition of the thorium material to allow for regular, routine milkings capable of supplying up to 3.7 GBq (100 mCi) of radiochemically pure Ac-225 annually. This routine separation is accomplished using a combination of anion exchange chromatography to separate Ac and Ra isotopes from Th and extraction chromatography employing TEVA and DGA-N resins to separate actinium from radium and breakthrough thorium.