A major success story at Oak Ridge National Laboratory is arguably more amazing than most “treasure from trash” stories. It is about a company that continuously extracts from a potentially dangerous nuclear waste at ORNL a radioisotope that offers hope to cancer patients in clinical trials.
The radioisotope is called thorium-229, and a product of its decay chain is the medically valuable, potentially life-saving isotope actinium-225.
Decay of actinium-225 triggers the release of highly energetic alpha particles. They are key to promising treatments of pancreas, prostate and colon cancers, among others. Such targeted alpha therapy (TAT) can destroy tumor cells’ DNA without harming cancer patients’ normal cells.
The nuclear “trash” at ORNL known as uranium-233 is highly hazardous, highly radioactive and highly fissionable material from U.S. Department of Energy sites.
Isotek Systems LLC, a wholly owned subsidiary of AtkinsRealis US Nuclear, manages the safe storage and disposition of the uranium-233 after it is processed and thorium-229 is extracted from it for medical uses, said Sarah Schaefer, president and project manager of Isotek Systems. She gave a talk to Friends of ORNL earlier this year. The subsidiary is prime contractor to DOE’s Oak Ridge Office of Environmental Management (OREM).
She announced two major accomplishments of Isotek Systems at ORNL during her FORNL talk, which was titled, “Reducing ORNL Risks and Preserving a Critical Isotope.”
In March 2026, Isotek Systems had extracted nearly 21 grams of thoriumIs-229 from uranium-233 at ORNL that was loaded into the roughly 250 canisters. This tiny amount, three-quarters of an ounce, boosted the global supply of thorium-229 by more than 2,000% halfway through Isotek’s processing campaign.
“That is about 90% of the available thorium in the uranium material still left at ORNL before it is shipped for permanent disposal,” Schaefer told the FORNL audience.
She also announced that in March half of the remaining uranium-233 inventory had been processed and disposed of. The entire job is expected to be completed in 2031.
To render the uranium-233 proliferation-resistant, Isotek personnel work in heavily shielded hot cells to “downblend” the highly enriched fissile material. After dissolving the uranium-233 in nitric acid, they mix it with depleted uranium-238, making it low-enriched. After being solidified in cement and loaded into canisters, the downblended uranium-233 is safer to transport and permanent disposal out of state.
Schaefer said Isotek employs 185 persons on the ORNL campus. The staff she leads consists of 80% AtkinsRealis personnel and 20% key subcontractors, many of whom have expertise in nuclear safety, nuclear criticality and uranium-233. She noted that Isotek has many partners, including Tennessee Tool & Engineering of Oak Ridge, which fabricated much of the equipment Isotek uses.
She told about the two buildings where the Isotek staff work, ORNL Buildings 3019 and 2026.
The uranium-233 is stored in Building 3019, which was originally constructed in 1943. It was used to extract the first milligrams of plutonium from the irradiated uranium slugs removed from the Graphite Reactor, the world’s first operating nuclear reactor, which was built during World War II. In 1962 Building 3019 became a repository for uranium-233.
Building 2026, which was constructed in the 1960s for the characterization of highly radioactive materials, was refurbished in 2017 for use in processing uranium-233.
Schaefer said uranium-233 is a manmade material produced by neutron bombardment of thorium-232 in reactors. It was explored as a potential reactor fuel.
Most of the highly radioactive material shipped to ORNL for storage was produced in the 1950s and early 1960s by reactors at Hanford, Washington, and the Savannah River Site in South Carolina. The uranium-233 inventory at ORNL was deemed unsuitable for further use because it was contaminated with uranium-232, which decays to thallium-208, a strong, hazardous gamma ray emitter.
From the 1960s to the 1990s, more than 1,000 canisters of most of the uranium-233 inventory in the United States was transferred to Building 3019, Schaefer said. From 2011 to 2017, she added, Isotek personnel reduced the uranium-233 inventory in half during the Direct Disposition Campaign.
Since 2019 the remaining uranium-233 inventory at ORNL has been “mined” for the world’s supply of the source of actinium-225, an alpha emitter that has a 10-day half-life, making it ideal for clinical trials for cancer patients. That parent isotope is thorium-229, the daughter product of the decay of uranium-233. In contrast, uranium-233 has a half-life of 160,000 years and thorium-229 has a half-life of 7,340 years.
In the early 1990s, an Iranian-American nuclear medicine researcher at ORNL named Saed Mirzadeh led an isotopes group in piloting the separation of thorium-229 from uranium-233. His award-winning, pioneering work produced actinium-225 from the decay of thorium-229 and led to his collaboration with medical researchers in an extensive investigation. It included multiple clinical trials in several treatment centers, some of which used a promising TAT agent for treating several types of cancer.
Targeting alpha therapy involves attaching an alpha-emitting radioisotope like actinium-225 to a molecule such as a monoclonal antibody in a chelator that, somewhat like an armed guided missile, seeks out and binds specifically to receptors on the surface of cancer cells. As the isotope decays quickly, it releases highly energetic alpha particles that inflict lethal radiation damage on cancer cells but spares healthy cells.
Schaefer said Mirzadeh’s group extracted less than a gram of thorium-229 but produced the actinium-225 by “milking” the thorium-229 in a “thorium cow” they devised to allow it to decay to radium-225, which decays to actinium-225. Until two years ago, ORNL was producing most of the actinium-225 available and pushing the TAT research. Isotek scaled up the ORNL thorium extraction technology based on the successes of Mirzadeh and his colleague Rose Boll.
TerraPower, started by Microsoft founder Bill Gates, approached DOE because it was committed to saving the remaining thorium-229 for its potential medical value. In 2018 a powerful public-private partnership was formed by DOE-OREM, Isotek Systems and TerraPower Isotopes because of TerraPower’s offer to provide funding for Isotek to buy the equipment needed for scaled-up thorium extraction.
Since 2019, TerraPower Isotopes has been paying Isotek to extract thorium-229, and the company was able to begin producing actinium-225 from that material two years ago. Schaefer noted the earnings have funded refurbishment of additional hot cells in Building 2026, while reducing the cost of disposing of uranium-233, saving taxpayers millions of dollars.
TerraPower Isotopes will ultimately receive from Isotek up to 45 grams of thorium-229 (less than one-and-a-half ounce), which TerraPower Isotopes will supply to their partners who will produce their own actinium-225 in hot-cell facilities. These partners will refine their TAT techniques for use in various clinical trials - phase1 through phase 3 - for cancer patients.
According to Schaefer’s slideshow, Bristol Myers Squibb and RayzeBio are farthest along (in phase 3) with their testing of their TAT technique on pancreatic cancer patients in clinical trials. Their treatment may be ready for the market in 2027.
Other companies making progress in using TAT on patients are Novartis (prostate cancer), AstraZeneca/Fusion (prostate cancer and solid tumors), Convergent Therapeutics (prostate cancer), Bayer (prostate cancer), City of Hope (colorectal cancer) and Ratio Therapeutics (sarcomas – malignant tumors of connective tissue).
A question came up about whether the amount of thorium extracted would meet the demand for TAT using actinium-225 derived from thorium-229 decay. Schaefer said the “market will be driven by the number of successful clinical trials because that will determine the number of patients who want the approved therapy.”
She noted that “10% of uranium-233 material in the United States had been transferred to other DOE programs, and there are preliminary discussions now of potentially bringing that material back to ORNL. Isotek could then extract up to eight grams of thorium from the returned material while processing it for disposal.”
If TerraPower Isotopes experiences great demand for the 45 or more grams of thorium-229 purchased from Isotek, Schaefer said, the growing need “will drive future research into how to generate actinium-225 directly” by using accelerators or other technologies.
At the meeting, former FORNL president Jim Rushton said that in 1994 the U.S. Defense Nuclear Safety Board was trying to determine what to do with the uranium-233 inventory at the lab. At the time he was leading the dismantlement of ORNL’s Molten Salt Reactor Experiment, which had produced uranium-233 by transmutation of thorium-232 through neutron capture. Also in 1994, Mirzadeh was pioneering thorium extraction from uranium-233 in Building 3019.
“DOE had to come up with a comprehensive management plan for Building 3019, which had received uranium-233 from MSRE (Molten Salt Reactor Experiment) and from around the country,” Rushton told Schaefer. “What you all at Isotek have done is just amazing. This is a major accomplishment. Congratulations!”
