The field of players vying to become the first domestic US producer of molybdenum-99, the parent isotope to the most widely used medical radioisotope, has become crowded. So, too, has the Missouri research reactor where three of them will access the neutrons they need to produce it.

The University of Missouri Research Reactor will provide irradiation services to three of the four prospective producers of molybdenum-99 in the US. The core of the 10-MW reactor, one of the last in the US to be fueled by highly enriched uranium, glows blue as the result of Cherenkov radiation.

The University of Missouri Research Reactor will provide irradiation services to three of the four prospective producers of molybdenum-99 in the US. The core of the 10-MW reactor, one of the last in the US to be fueled by highly enriched uranium, glows blue as the result of Cherenkov radiation.

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Three businesses will each receive up to $25 million in funding from the US Department of Energy’s nonproliferation program to develop their distinct processes. They must match the government’s support with their own investment. At least seven other firms that aren’t participating in the DOE program say they hope to produce 99Mo in the US.

According to a 2014 report from the Organisation for Economic Co-operation and Development’s Nuclear Energy Agency, worldwide demand for 99Mo is about 520 000 six-day curies per year. The US accounts for about half of that. A six-day curie is a measure of the remaining radioactivity of 99Mo six days after it leaves the processor’s facility.

Three hopefuls have signed agreements with the University of Missouri Research Reactor (MURR) for neutron irradiation services. Ironically, MURR is one of only two remaining US university reactors that are fueled with highly enriched uranium (HEU) (see Physics Today, January 2014, page 24). The explicit goal of the DOE funding program is to establish domestic sources of 99Mo that don’t use HEU, from which nuclear explosives could be fashioned. Although the 10-MW MURR will eventually be converted to low-enriched uranium (LEU), that isn’t expected to occur until the mid 2020s, once DOE designs and produces an LEU fuel that will provide the same neutron flux as the HEU fuel.

With a 66-hour half-life, 99Mo decays to metastable technetium-99, which has a 6-hour half-life and is used in 80% of the world’s nuclear medical imaging procedures.

Two Wisconsin businesses, NorthStar Medical Radioisotopes and Shine Medical Technologies, are pursuing three different technology paths to 99Mo production. NorthStar appears on track to be the first US producer to market. It’s the only one of the DOE participants that will produce material by neutron capture—that is, irradiating targets containing 98Mo. The other two will fission uranium-235 to obtain the isotope.

James Harvey, NorthStar’s chief science officer, says that he expects MURR-generated 99Mo sales to commence in the second quarter of 2016—more than a year ahead of competitors—pending approval from the Food and Drug Administration. The timing will coincide with a “market vulnerability” that will develop around that time, when a Canadian reactor is due for its annual maintenance shutdown lasting two to four weeks. A Belgian reactor that produces 99Mo is currently shut down for maintenance and is expected to remain off-line through April or May, Harvey says.

But NorthStar has been overly optimistic in the past. A March 2011 company press release stated that shipments to pharmacies would begin later that year.

In September of this year, NorthStar signed a memorandum of understanding with Westinghouse Nuclear to explore the use of neutron capture for 99Mo production in Westinghouse’s pressurized water reactors. NorthStar is also developing an accelerator-driven production process that will work by knocking a neutron out of 100Mo. The company expects to begin producing accelerator 99Mo in 2017. The combined output from its two processes could satisfy 100% of US demand, according to Harvey.

So far, DOE has provided $16 million for NorthStar’s fission process and $5 million for its accelerator R&D.

Shine won’t be using MURR. It’s pursuing a hybrid route in which deuterium from an accelerator beam fuses with tritium gas, explains company CEO Gregory Piefer. The resulting high-energy neutrons fission the 235U in LEU targets, producing 99Mo. The company is operating a full-scale accelerator using only deuterium.

Piefer says fundraising has slowed progress toward building a production plant, which is estimated to cost $100 million. “If we are able to get major commitments, either in the form of a 50-50 match from the government or from the private sector, 2018 is still possible, but [funding] would have to happen pretty quickly, in the next several months.” The venture has received around $15 million from DOE to date.

Northwest Medical Isotopes, which hasn’t requested DOE funding, will break ground on its processing facility adjacent to the University of Missouri campus as soon as it receives Nuclear Regulatory Commission approval, says Nicholas Fowler, CEO. He expects that to occur early in 2016. Construction should be completed in 12–18 months, and a short production qualification period will follow before full production begins. The company has arranged to use several other research reactors, including that at Oregon State University, which is a partner in the business.

Fowler says multiple reactors will address the Achilles heel of 99Mo development: the reliance on too few sources. “No matter how reliable—and MURR has a fantastic reliability schedule—having a network of university reactors enables us to balance the supply,” he says. “It also allows us to have multiple shipments within a week if we want it.”

The newest entry to the government-sponsored field is General Atomics of San Diego, in partnership with Nordion, the Canadian firm that currently manufactures 99Mo from targets fabricated with US-supplied weapons-grade uranium. Nordion, the major US supplier, has irradiated its targets in Canada’s National Research Universal reactor (NRU) at Chalk River Laboratories in Ontario. The 58-year-old facility was scheduled to be closed permanently next year, but the Canadian government announced last February that it would extend its operation for another 18 months, through March 2018, if market conditions warrant. On 30 September DOE announced a $9.7 million award to General Atomics.

Christina Back, General Atomics vice president, says its process will expose LEU targets to an extraction gas at MURR. During irradiation, a gas-phase form of 99Mo and volatile fission products are removed from the targets. Gas recirculation results in continuous output of 99Mo until the target is depleted and needs replacement about once a year. No dissolution of the irradiated targets is necessary to recover 99Mo, so the waste stream is minimized, Back says. Commercial sales are expected in about two and a half years.

Ralph Butler, MURR executive director, says the reactor has the capacity to meet the needs of the three producers. The operation will not adversely affect MURR’s research activities, although the fission-based operations will displace some of the materials irradiation work performed for industry.

Last year MURR produced 35 isotopes, used primarily for research. The reactor also provides active ingredients for two FDA-approved radiopharmaceuticals, he said, the output of which shouldn’t be affected by 99Mo work.

If each of the 99Mo businesses achieves viability, their combined output would meet the US demand twice over. Since exports are difficult due to the isotope’s lifetime—the rule of thumb is about 1% of 99Mo is lost each hour, says Piefer—a market shakeout would likely ensue.

But each contender asserts it will be the lowest-cost producer. Piefer notes that 99Mo produced through fission contains a much higher specific activity—50 000 curies per gram—than the 1–10 curies per gram of the NorthStar neutron-capture material. That’s because chemically separating Mo from U targets is straightforward, but isolating Mo isotopes from each other is too time-consuming and impractical, given the lifetime of 99Mo.

For that reason, NorthStar’s pharmacy customers will need a chromatographic separation device installed onsite to tap the technetium-99m. Harvey says the product will have the same specific activity as the fission-based 99mTc. He adds that NorthStar won’t have to pay for disposal of the high-level nuclear waste from the fission processes.

Says General Atomics’s Back: “We think we have advantages because we will have solid waste and low specific production costs with low capital investment.” And, she adds, “We think we’ll be more efficient than the accelerators.”

Other firms with plans to make 99Mo in the US without government backing include Coqui RadioPharmaceuticals, Flibe Energy, NuVue Therapeutics, Perma-Fix Medical, Eden Radioisotopes, and Niowave. Coqui CEO Carmen Bigles says the company expects to begin commercial production in 2020, using neutrons that are generated in a reactor it plans to build in Alachula, Florida. The open-pool reactor will be similar to Australia’s Open Pool Australian Lightwater (OPAL) research reactor, which also produces 99Mo. Bigles says DOE declined its request for funding because Coqui’s process uses proven technology.

Two past recipients of DOE nonproliferation funding, GE-Hitachi and Babcock and Wilcox, have suspended their 99Mo development efforts.