A South African company in December 2010 became the first of the world’s four major processors of molybdenum-99 to ship a commercial quantity of the medical radioisotope that was manufactured without the use of highly enriched uranium (HEU). The milestone was reached with help from the US Department of Energy (DOE), which is providing $25 million to help the South African Nuclear Energy Corp (Necsa) rid its 99Mo production process of HEU, which poses a nuclear proliferation risk due to its concentration of fissile 235U. DOE, however, continues to provide HEU to the Canadian 99Mo manufacturer, Nordion, which, like Europe’s two producers, has no immediate plans to convert its processes to low-enriched uranium (LEU).

With a half-life of 66 hours, 99Mo is used in 80% of all nuclear medical procedures. In the US, roughly 16 million patients a year undergo procedures that employ its decay product, metastable technetium-99m. With a six-hour half-life, 99mTc is the preferred radioactive tracer, or imaging agent, in most radiopharmaceuticals that are targeted to particular organs or specific kinds of cells. An imaging technique known as single-photon-emission computed tomography is used to assemble a three-dimensional image from the radiation collected by a rotating gamma camera. Although the US consumes half the world’s output of 99Mo, it has no domestic producer.

Necsa’s shipment marked a first, but the company won’t be converting fully to LEU operation until 2014, says Don Robertson, managing director of Necsa subsidiary NTP Radioisotopes. Much of the delay is due to the need to obtain the necessary regulatory approvals and to get material produced with LEU qualified for patient use in multiple countries, he and other producers say.

The SAFARI-1 research reactor operated by the South African Nuclear Energy Corp is one of only five major reactor sources of molybdenum-99, the radioisotope required for four-fifths of all nuclear medicine procedures.

The SAFARI-1 research reactor operated by the South African Nuclear Energy Corp is one of only five major reactor sources of molybdenum-99, the radioisotope required for four-fifths of all nuclear medicine procedures.

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Technicians at NTP Radioisotopes, a subsidiary of the South African Nuclear Energy Corp, preparing molybdenum-99 in hot cells at the production complex.

Technicians at NTP Radioisotopes, a subsidiary of the South African Nuclear Energy Corp, preparing molybdenum-99 in hot cells at the production complex.

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The National Nuclear Security Administration, a semiautonomous unit of DOE, has offered to assist the world’s other three major 99Mo producers in moving to LEU processes, but none have accepted yet, says Parrish Staples, an NNSA program manager. The US offer was reiterated during the April 2010 nuclear security summit convened by President Obama, at which 47 heads of state signed on to Obama’s campaign to gather and secure by the end of 2014 all HEU that remains in civilian hands. (See PHYSICS TODAY,July 2010, page 24.) “[NNSA’s] basic mandate for HEU minimization is to provide assistance to all global producers to eliminate the use of HEU in medical isotope production,” says Staples.

Necsa provides about 20% of the world’s 99Mo output under normal market conditions, Robertson says. Commissioned in 1965, Necsa’s SAFARI-1 reactor operated for most of its life on HEU fuel but was converted fully to LEU in 2009. The more difficult challenge for 99Mo producers has been to remove HEU from the targets that are irradiated inside the reactor. “From a purely technical standpoint, using HEU is more efficient,” Staples acknowledges. But advances in technology offer alternative methods for concentrating the amount of 235U in targets. “LEU target development is similar to fuel development, where we try to provide the same number of uranium-235 atoms inside the cladding as a normal fuel element,” he says. “We try not to change the physical structure of the facility at all, but simply through advances in metallurgy and analysis to maintain the capacity of the reactor using LEU instead of HEU.”

Converting from HEU has negatively impacted the economics, Robertson says, since lower enrichment generally means less 235U in the targets. “We are on the order of 10–20% lower on the uranium-235 loading in our targets.” Necsa believes that the LEU production process will about double the amount of waste generated in extracting the isotope, says Robertson. Other producers are likely to see a factor of four increase in their wastes.

Pressure from the US to eliminate all commercial uses of HEU is occurring against a backdrop of severe shortages in the supply of 99Mo in recent years. There are only five reactors in the world—each around 50 years old—producing material for four processors. A prolonged shutdown of one reactor, as occurred for 15 months at Canada’s National Research Universal (NRU) facility, is sufficient to create havoc with nuclear medicine worldwide (see PHYSICS TODAY,May 2008, page 22). The NRU routinely produces 30% of the world’s 99Mo, but it’s capable of generating as much as 80% if necessary, says Jill Chitra, senior vice president for quality and regulatory affairs at Nordion, an Ottawa company that purifies and distributes the NRU’s 99Mo. “There is no reactor in the world that can replace NRU’s capacity,” Chitra asserts.

The NRU shutdown was followed by the idling of the second largest reactor source, the High Flux Reactor in Petten, the Netherlands, for more than half of 2010 for scheduled maintenance and repairs. Taken together, the NRU and the HFR account for more than half of the global supply. During their outages, two of Nordion’s competitors, Covidien, which processes 99Mo in the Netherlands, and Belgium’s Institute for Radioelements, found research reactors in Poland and the Czech Republic willing to supply some of the lost isotope. Necsa also stepped up its output during the supply crunch, and at times it was the only producer operating, Robertson says.

Although SAFARI-1 is about the same age as the HFR and the NRU, Robertson points out that the Necsa reactor had been virtually mothballed for 10 years when economic sanctions were imposed on South Africa to force an end to apartheid. As a result, it is a relatively younger machine than the others, and Robertson anticipates many more productive years of operation.

Staples says DOE is well aware of the need to maximize medical isotope production as conversion from HEU operations occurs. But he insists that conversion to LEU can be accomplished without a significant reduction in capacity. Today’s 99Mo targets consist of HEU dispersed in an aluminum powder. Simply replacing some of the aluminum with LEU will increase the density of 235U in targets and hence 99Mo output, he says. Further gains in efficiency can be achieved if a uranium metal foil that DOE has developed for targets can be scaled up. Use of the foil could also significantly reduce the volume of processing wastes.

Nordion is prepared to convert its processes to accommodate LEU targets as soon as they become available, Chitra says. Nordion currently receives all its material from the NRU operator, state-owned Atomic Energy of Canada Ltd (AECL). The processing technology varies depending on whether HEU or LEU targets are irradiated.

The Canadian government has stated that the NRU will be closed for good in 2016. What happens after that is unknown, says Chitra. Nordion is in litigation over AECL’s 2008 decision to terminate construction of two reactors that were supposed to replace the NRU and provide a backup to each other. The new units were to be LEU fueled, although their targets were designed to use HEU. The partially built reactors were abandoned after major design flaws were discovered.

Nordion recently contracted with Russia’s State Atomic Energy Corp, Rosatom, to supply 99Mo during an NRU shutdown scheduled for this May. The agreement also calls for Russia to supply up to 20% of the Canadian firm’s isotope requirements beginning in 2016. The material is to be produced by JSC State Scientific Center–Research Institute of Atomic Reactors, which operates three research reactors near Moscow. Those units are presently HEU fueled but are to be converted with US help under an agreement signed by DOE and Rosatom officials on 10 December 2010. Nordion is evaluating other potential sources, including Canada’s TRIUMF linear accelerator facility in Vancouver. Initial samples of 99Mo derived from LEU targets irradiated at TRIUMF are expected in 2012. Chitra estimates that a linac source could produce about 30% as much as the NRU.

Before the Canadian dual-reactor project collapsed, the US government saw little reason for a domestic source. Now, spurred on by the shortages, DOE is working with four US industry teams to develop different technological paths to isotope production. Each project is eligible for up to $25 million in DOE funding, provided taxpayer funds are matched with private money, says Staples. GE Hitachi Nuclear Energy is pursuing a nonfission route in which a target’s 98Mo atoms capture a neutron to become 99Mo. Babcock and Wilcox, in partnership with Covidien, proposes a fission process in which the LEU is dissolved in a solution of water and acid. The company claims its system simplifies the extraction process, allows reuse of uranium, and is inherently passively safe.

The other two novel production processes were selected by DOE from proposals submitted in response to a 2010 solicitation. NorthStar Nuclear Medicine proposes the use of gamma rays to bombard a 100Mo target and produce 99Mo via a gamma–neutron reaction. And the Morgridge Institute for Research in Madison, Wisconsin, is heading an effort to fission uranium contained in a liquid target with neutrons generated in an accelerator. Each company was awarded $500 000 initially.

The effort by DOE has proceeded despite Congress’s failure to explicitly authorize an agency program to stimulate domestic supply. A bipartisan bill, the American Medical Isotopes Production Act, was approved by an overwhelming margin of 400–17 by the House in 2009, but it was blocked from a Senate vote by former senator Christopher Bond (R-MO). The bill would have authorized DOE to spend $163 million over five years to help create a domestic industry and would have ordered an end to all US HEU exports over a 7- to 13-year period. Bond was worried that the measure might ban the importation of medical isotopes that were produced with HEU.

The University of Missouri operates one of the few remaining US reactors to be fueled with HEU. It is also the most powerful university research reactor in the US. It produced 99Mo from 1967 to 1984 and is capable of meeting about half of US demand. While university officials have expressed interest in getting back into the business, they reportedly are unwilling to commit academic funding to obtain DOE cost sharing. Cost estimates to build a 99Mo processing facility range as high as $150 million.

In Canada, the government is supporting development of accelerator-based production processes with a combined Can$35 million ($34.6 million). The government has said it is interested in meeting only Canadian demand for 99Mo following closure of the NRU. The Dutch Nuclear Research and Consultancy Group, which operates the HFR, is planning a replacement reactor that could come on line around 2020 if funding can be found. That reactor, named Pallas after a Greek goddess, would be fueled with LEU and would accommodate either LEU or HEU 100Mo targets.