ORNL's medical radioisotope project sees centennial campaignBill Cabage
June 15, 2012
Karen Murphy and Greg Groover work at ORNL's Radiochemical Engineering Development Center, where the thorium-229 and actinium-225 is processed for medical uses.
One of ORNL's most celebrated "trash to treasure" projects is observing a centennial. The Laboratory's Nuclear Medicine Program is in its 100th campaign of thorium-229 and actinium-225 processing, which provides radioisotopes for medical uses that include cancer treatment.
Actinium-225 is a source for bismuth-213, a short-lived, alpha-emitting radioisotope that is used to treat cancer. Because bismuth-213 is so radiologically short-lived -- less than one hour's half life -- it must be shipped in the form of its parent radionuclide, actinium-225, which has a 10-day half life. At the clinic, the "daughter precursor" bismuth-213 is then "milked" from a biomedical generator device and immediately used for treatment for maladies such as acute myeloid leukemia.
The bismuth radioisotope, when combined with tumor-seeking monoclonal antibodies, homes in on cancer cells, zapping them with a lethal shot of alpha radiation while leaving healthy cells unaffected.
The ultimate source of this medical radioisotope is uranium-233. Since starting in 1995, ORNL researchers, led by Saed Mirzadeh in the Nuclear Medicine Program, have developed and refined a process to transform surplus U-233 through a chain of daughter isotopes -- thorium 229 to actinium-225, which is shipped to clinics.
By 1997, ORNL was and still is the world's major supplier of high-purity actinium-225 for applications in targeted alpha therapy.
It all began in the 1960s with the Molten Salt Reactor Experiment, when uranium-233 for the MSRE project was produced by irradiating thorium targets in nuclear reactors. After extracting uranium-233 from the target, the thorium target together with the thorium-229 byproduct and other fission products were stored in tanks at ORNL.
In 1994 about a third of the sludge from the MSRE waste tanks -- the "trash" -- was sold to a Netherlands firm and eventually sent to the Institute for Transuranium Elements in Karlesruhe, Germany, for research. Mirzadeh had been trying to get access to the thorium for some time, and the next year he, Steve Kennel and Kenneth Givens received funding to extract the thorium from the waste sludge.
Ensuing biological research demonstrated that bismuth-213 derived from the thorium efficiently killed cancer cells in mice. Then followed clinical trials, including at the Memorial Sloan Kettering Cancer Center, where bismuth-213 was used in clinical trials of leukemia treatments. Other batches went to the National Institutes of Health and to universities.
Mirzadeh explains the process: "Every 60 days we milk the radium from thorium-229, which has already been separated from uranium-233 stock, and we separate actinium from the radium weekly. After 60 days the radium is depleted and we repeat the process. It takes about a week to milk the thorium. The resulting actinium is purified, subjected to the proper quality controls and then shipped to a clinic, where is it processed into bismuth-213 for treatments. We start on a Monday, and ship the following Monday. That's a campaign."
The work, which requires facilities equipped for working with alpha radiation to medical standards, was originally done in hot-cell labs on the main ORNL campus, but is now done in ORNL's Radiochemical Engineering Development Center. The process has seen ongoing improvement of its output, which is fortunate because ORNL is the only source of the valuable radioisotope.
"There is no waste; we control every aspect," Mirzadeh says.
Still, because of limited supplies of thorium and the inability to produce enough bismuth-213 to meet demand, the nuclear medicine team has turned its attention to using its precursor, actinium-225, directly to take advantage of its more manageable 10-day half-life, which also better matches the lives of the targeting molecules that deliver the radioisotope to the cancer cells. Because less isotope is required to treat patients, the extra actinium-225 has been used in other clinical trials and in development of actinium-225 to bismuth-213 generators for clinical use.
Mirzadeh's current research focuses on the potential application of inorganic nano-material as a means of trapping actinium-225 and associated daughter products to mitigate their unintentional release in vivo.
Mirzadeh credits a number of ORNL researchers, managers, craftsmen and technicians who have made the actinium program work, often, he says, "through sheer dedication and ingenuity." He singles out project leader Rose Boll at the Radiochemical Engineering Development Center, who joined the project in 1996 as a postdoc and developed the processing chemistry, as an "invaluable" member of the team. Major credits also go to two three outstanding technical staff; Karen Murphy, Greg Groover and Linda Farr, who have operated the process for the past 15 years safely and efficiently "with 100-percent customer satisfaction and on-time delivery."
ORNL's medical isotope program has been supported through the years with funding from DOE's Office of Nuclear Energy and Office of Nuclear Physics.
The waste-thorium to treasure-actinium program's 100th campaign could be measured in saved lives or mitigated suffering. It's certainly a measure of the radiological capabilities and chemistry know-how of the ORNL staff.— Bill Cabage, June 15, 2012