US-based TerraPower Isotopes (TPI) is now producing Actinium-225 (Ac-225) at commercial scale, supplying it to the global pharmaceutical community through weekly production runs. The Actinium, after further manufacturing, is now used in multiple drug developers’ radiopharmaceuticals for human clinical trials worldwide.

“This scale up of production capacity of TerraPower Isotopes Actinium-225 opens a new chapter in the development of cancer treatment options, and I’m proud to be part of the journey,” said TPI President Scott Claunch. “We are proud to be the first company to provide Actinium-225 at this scale, transforming how the pharmaceutical industry approaches cancer treatment with targeted alpha therapies.”

TPI uses a natural decay method to produce Ac-225 free of isotopic impurities. This method increases the efficiency and automation of the process, which enables TPI to produce a significant, consistent supply of the isotope to the market.

Ac-225 is used as a starting material for research and development of advanced, targeted cancer treatments and in drug trials involving targeted alpha therapy. The isotope can be attached to a molecule, which can then selectively target and deliver Ac-225 to the cancer site to potentially treat diseases such as prostate, breast, colon and neuroendocrine cancers, melanoma and lymphoma with minimum damage to nearby healthy cells.

The TPI team works with the US Department of Energy’s (DOE’s) Oak Ridge Office of Environmental Management (OREM) and AtkinsRéalis subsidiary Isotek Systems to increase the supply of Ac-225 by harvesting the isotope from thorium-229 (Th-229) decay. In November 2019, TerraPower, Isotek Systems and DOE signed a public-private partnership agreement under which Isotek extracts Th-229 from Uranium-233 (U-233) stored at Oak Ridge National Laboratory (ORNL), which TerraPower then uses for the production of Ac-225.

Since 2003, Isotek has been contracted by the DOE to oversee the inventory of U-233, a legacy of Cold War-era operations, and prepare its removal from ORNL’s Building 3019, the nation’s oldest operating nuclear facility. U-233 was originally created in the 1950s and 1960s for potential use in reactors but proved to be an unviable fuel source.

In 2020 Isotek Systems and DOE signed a contract modification to perform processing operations for disposition of the U-223 until 2024. This contract modification authorised $254m to fund and continue Isotek’s mission to safely dispose of more than 80% of the remaining U-233 inventory.

In June, OREM and Isotek surpassed DOE’s goal of processing 35 canisters of U-233 in 2024. They had processed 39 canisters, bringing the total to 100 canisters processed as part of the U-233 Disposition Project.

Half of the U-233 inventory was disposed of between 2011 and 2017. However, the remaining material requires processing to convert it into a form safe for shipment and disposal. “Getting to this point has taken a lot of hard work,” said Sarah Schaefer, Isotek President & Project Manager. Isotek began processing the lower-dose material in 2019 and higher-dose material in 2022. The current processing campaign for the higher-dose material is 25% complete and slated for completion in 2026. Isotek employees are processing the higher-dose uranium-233 in hot cells into a form safe for shipment and disposal.

Researched and written by Judith Perera