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Radiopharmaceutical production in the face of nuclear nonproliferation

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Radiopharmaceutical production in the face of nuclear nonproliferation

Mechanical engineering Associate Professor Gary Solbrekken and Casey Jesse, a graduate student in mechanical engineering work in Solbrekken’s lab.

According to the World Nuclear Association, approximately 90 percent of nuclear medicine procedures conducted worldwide are diagnostic in nature and fully 30 million of them utilize the radioisotope technetium-99m (Tc-99m). More than half of these procedures occur in the United States, and for nearly a decade, there has been an international effort to ensure that a reliable and safe supply is available.

Currently, up to 95 percent of the world’s molybdenum-99 (Mo-99), the parent isotope of Tc-99m, is extracted from nuclear weapons grade, highly enriched uranium (HEU)-based targets. Mo-99 is produced by irradiating these targets in a nuclear reactor. Five large-scale producers are responsible for a majority of the world’s Mo-99 supply, with facilities located in Canada, the Netherlands, Belgium, Australia and South Africa.

A primary goal of the Department of Energy National Nuclear Security Administration’s (NNSA) Global Threat Reduction Initiative (GTRI) is to convert civilian research reactors and radiopharmaceutical production facilities worldwide from HEU to low-enriched uranium (LEU).

At the Nuclear Security Summit in Seoul in late March of this year, Belgium, France, the Netherlands and the United States agreed, subject to regulatory approvals, to support conversion of European Mo-99 production facilities to non-HEU-based processes by 2015.

“That’s where we come in,” said University of Missouri mechanical engineering Associate Professor Gary Solbrekken of the growing international commitment to nuclear nonproliferation goals.

Charlie Allen, the University of Missouri research reactor’s Mo-99 project manager, is collaborating with Associate Professor Gary Solbrekken to develop low-enriched uranium targets for the production of radiopharmeceuticals.

Since 2006, the University of Missouri’s Research Reactor (MURR) Center has been working to develop a new LEU target design that will replace the current HEU target. The purpose of the LEU target is to not only produce Mo-99 without the use of HEU, but also to maintain the current Mo-99 yield per target. Collaborating with Charlie Allen, MURR’s Mo-99 project manager, Solbrekken has received in excess of  $1 million in funding since 2009 from Oak Ridge Associated University (ORAU), the Department of Energy’s Y-12 National Security Complex (Y-12) and The Department of Energy’s Argonne National Lab (ANL) to develop LEU targets.

“Depending on what pharmaceutical Tc-99m is tagged to, the isotope will concentrate in different parts of the body where it can be imaged by physicians,” Solbrekken explained.  “It has a half-life of approximately six hours, which makes it attractive when working with biological systems because you want it to decay and get out of the system as quickly as possible.”

With a half-life of six hours, Tc-99m’s rapid decay makes stockpiling and transporting necessary quantities unrealistic, thus Mo-99 with its 66-hour half-life is used to allow for limited stockpiling and transportation over greater distances.

The process

Traditionally, the production of a Mo-99 target involves mixing HEU powder with aluminum powder and encapsulating the mixture within an aluminum envelope, or plate, called cladding. The target is placed in a nuclear reactor and bombarded by neutrons — irradiated — and once removed, the entire target is dissolved in a chemical bath to extract Mo-99 and other radioisotopes.

“The dispersion target (powder target) has great bonding, is exceptionally strong, and it cools quickly; it’s a proven technology,” Solbrekken said of Mo-99 production using HEU.

Satisfaction with established methodologies is only one reason there is resistance on the part of radiopharmaceutical production facilities to switch to LEU. It is estimated that there will be a slight increase — less than 10 percent — in the cost to produce Mo-99 using LEU, but reactor facilities would have to be retrofitted to accommodate new LEU- based isotope production, adaptations that potentially could carry large price tags.

“Producers must make a profit. They will convert when it becomes cost effective,” Solbrekken said, adding that the main focus of GTRI is on the conversion of the Mo-99 production to non-HEU based methodologies. “Working with a variety of entities, each with their own unique goals, has created an interesting tension between business, politics and technology.”

In addition to a change in the target design, there must be an adaptation to the current cooling areas and containment equipment used for chemical recovery and processing.

Solbrekken’s investigations into successful irradiation processes to produce Mo-99 using LEU have convinced him and his research collaborators — Y-12, ANL, MURR and the International Atomic Energy Agency (IAEA) — that foil targets consisting of a LEU foil and aluminum are the best alternative.

“We know it works, and it’s a good economic fit,” Solbrekken said of the procedures he and his team have developed.

Shown is a cut-away and close-up detail of a model of low-enriched uranium targets being developed and tested by Associate Professor Gary Solbrekken’s research group.

Solbrekken’s research group has been working with an aluminum annular (cylindrical) target in which a layer of high-density LEU foil, with a layer of nickel electroplated to both sides to keep the uranium from bonding to the cladding, is placed between the two aluminum cylinders of cladding. The target is assembled using pressure to ensure the bond is secure.

After the cylinder is irradiated, the cladding is removed and the nickel and foil are dissolved in a chemical bath to extract isotopes, a process similar to that of HEU targets.

“With this target design, it takes less time and energy to extract the Mo-99 from the target,” said Allen. “It takes less solvent to dissolve it, so there is less radioactive waste.”

An actual aluminum annular (cylindrical) target contains a layer of high-density LEU foil, with a layer of nickel electroplated to both sides to keep the uranium from bonding to the cladding. It is placed between the two aluminum cylinders — cladding — and the target is assembled using pressure to ensure the bond is secure.

The mechanical process of removing the cladding is being researched in the lab of Solbrekken’s Mizzou Engineering colleague, Professor Sheriff El-Gizawy.

But there are some challenges, especially since each country’s stringent safety regulations governing the production of isotopes are a key consideration.

“It’s tough to get the foil extremely thin. It has a tendency to tear,” Solbrekken said, adding that inconsistencies in the foil can cause problems, including the buckling of interfaces.

Doctoral student Kyler Turner is currently working in a Nonproliferation Graduate Fellowship with the National Nuclear Security Administration.

“Gasses produced by fission in an irregular target, like radioactive Xenon, can cause separation of the foil and the cladding, leading to an undesirable increase in the LEU foil temperature. The high temperatures in the target could cause failure releasing radioactive uranium, aluminum and other fission products into the reactor cooling system,” said Kyler Turner, a PhD candidate in mechanical and aerospace engineering, who earned both a master’s in mechanical and aerospace engineering and nuclear engineering from MU. He has been working with Solbrekken since 2007.

The research team has been using foils produced by Y-12 and the Korea Atomic Energy Research Institute. Produced using different methods, they each have advantages and disadvantages.

“We are working with Romanians [at the Pitesti reactor facility near Mioveni, Romania] on assembly techniques to expand the inner aluminum tube into the outer tube for a tighter fit,” Solbrekken said, adding that Allen has been instrumental in connecting him with collaborators around the world.

The team’s Romanian partners also are doing post irradiation examination (PIE) of the targets.

“During the PIE test, the Romanians will be examining the various foils after irradiation, investigating how their foils behave under irradiation,” said Turner, adding that this data will be instrumental in helping to persuade reactors producing Mo-99 with HEU to consider a switch to LEU.

“We know it works,” said Allen, echoing Solbrekken’s confidence in the foil targets and the annular geometry. “But no one has ever put together a test plan to use as objective evidence.”

Cold tests, with no radioactive materials have been conducted at MURR, as have a limited number of annular foil target irradiation tests.

Allen and Solbrekken agree that students on the research team can greatly benefit from the experience. Turner is participating in the Nonproliferation Graduate Fellowship with the NNSA’s GTRI in Washington, D.C., working on the development of non-HEU-based Mo-99 production both domestically and internationally. He heard about the position during summer internships at Y-12 in 2009 and 2010.

“Through my NNSA fellowship, I support the acceleration of non-HEU-based Mo-99 production methodologies,” Turner said. “I manage the funding we provide to the national labs to assist our commercial cooperative agreement partners, funding that allows them to access the immense knowledge base available in the DOE national lab system.

“The non-HEU-based Mo-99 production project has a great deal of high level governmental attention,” he said. “As part of my fellowship, I have had the opportunity to directly interact with representatives from the Office of Science and Technology Policy in the Executive Office of the President, the Nuclear Regulatory Commission and the Department of Energy. It’s a very interesting, fast-paced job, and living in Washington, D.C. has been an amazing experience.”

Because the production and use of Mo-99 for medical procedures and nuclear nonproliferation are highly visible issues of international importance, Solbrekken said the work has been personally gratifying.

“It’s not just an academic exercise. Our success means they [LEU foil targets] will be utilized in a real production facility, he said.

“I’ve never been interested in nuclear bombs and electricity. It didn’t dawn on me that there were so many other nuclear applications, like tracers in ground water, accelerators, cyclotrons and X-rays. As a mechanical engineer, these are things that really connect.”

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