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 ²²⁵Ac 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, ²²⁵Ac has been sourced from thorium/actinium generators based on the alpha decay of stockpiles of ²²⁹Th. ²²⁹Th is itself the alpha-decay product from ²³³U. Due to proliferation issues associated with ²³³U, 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 ²³³U stockpiles. A separation scheme for ²²⁵Ra and ²²⁵Ac 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 ²²⁵Ac 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.