Wisconsin company gets the green light to make key medical isotope

The first US production in 30 years of molybdenum-99, the parent isotope of the most widely used medical radioisotope, is expected to begin within weeks after federal regulators approved a manufacturing process developed by Wisconsin-based NorthStar Medical Radioisotopes.

On 8 February the Food and Drug Administration announced its approval of the process NorthStar will use to separate technetium-99m from ⁹⁹Mo. A ⁹⁹Mo decay product, ^99mTc is a gamma-emitting tracer used for roughly 40 000 nuclear medical imaging procedures daily. NorthStar officials say that they expect to have the capacity to meet two-thirds of US demand for ⁹⁹Mo.

NorthStar will be the world’s first producer to manufacture ⁹⁹Mo from feedstock other than uranium. Instead, the isotope will be created when neutrons from a reactor are captured by the naturally occurring ⁹⁸Mo isotope. Once the ⁹⁹Mo is chemically recovered, the company’s RadioGenix process will chromatographically separate injectable ^99mTc from a saline solution containing the three isotopes of molybdenum.

NorthStar’s solution contains the same amount of ^99mTc found in the uranium-based product, says James Harvey, NorthStar’s executive vice president and chief scientific officer. NorthStar’s FDA approval is valid only for production at the University of Missouri’s MURR research reactor; the company must obtain separate approvals for ⁹⁹Mo produced in other reactors.

Although the US consumes about half the world’s ⁹⁹Mo, the entirety of the nation’s supply is obtained from a handful of reactors in Europe, Australia, and South Africa. Planned and unscheduled reactor shutdowns have resulted in periodic and occasionally prolonged shortages of the isotope. In recent weeks, a South African reactor was shut down for regulatory reasons and an Australian producer had an unplanned five-day outage.

The ⁹⁹Mo supply chain also is fragmented. Processors obtain their material from different combinations of reactors. They then pass it on to other companies that manufacture and distribute devices known as technetium generators or moly cows to any of the US’s 350 radiopharmacies, which in turn supply hospitals with individual doses of ^99mTc.

The separation of ^99mTc in technetium generators near its point of use is necessary because of the isotope’s six-hour half-life. The half-life of ⁹⁹Mo is 66 hours, which means that the generators must be replaced weekly.

NorthStar officials say they can offer radiopharmacies assured supplies and pricing because the company controls the entire supply chain. The ⁹⁹Mo produced at MURR will be extracted and purified at NorthStar’s plant in Beloit, Wisconsin.

Stephen Merrick, NorthStar president, says the company will be able to meet 10% of US ⁹⁹Mo demand by the fourth quarter of this year. Production will ramp up to match two-thirds of US demand “within a few years.” The company will break ground next year on an accelerator facility that will produce ⁹⁹Mo by knocking off neutrons from targets containing ¹⁰⁰Mo.

NorthStar will be the first of three firms subsidized by the Department of Energy to begin production (see Physics Today, November 2015, page 20 ). The two other producer hopefuls are Shine Medical Technologies and a partnership between General Atomics and Canada’s Nordion. Shine plans to produce the isotope at its Wisconsin accelerator facility by fissioning low-enriched uranium (LEU) with high-energy neutrons created from deuterium–tritium fusion. GA–Nordion will irradiate LEU targets at the MURR. A recirculating gas will continuously capture ⁹⁹Mo and other fission products for separation. The process doesn’t require dissolution of uranium targets, which helps to minimize waste.

NorthStar received $25 million in matching funds from DOE for development of the neutron capture process and $14.8 million of an expected $25 million total for its accelerator approach. GA–Nordion and Shine are each expected to receive $25 million for their development processes.

Other companies have announced plans to produce ⁹⁹Mo without government assistance. They include Northwest Medical Isotopes, which plans to use MURR and a reactor at Oregon State University to irradiate LEU targets. The company is nearing Nuclear Regulatory Commission approval to construct a processing facility adjacent to the Missouri campus.

DOE was instructed by a 2012 law to stimulate creation of a domestic supply base for ⁹⁹Mo that doesn’t require highly enriched uranium (HEU). NorthStar’s production process doesn’t totally adhere: The MURR is one of two US university research reactors still fueled with HEU. The bulk of international commerce in HEU used for ⁹⁹Mo ended when production at Canada’s National Research Universal reactor, which had supplied about 40% of the US market, was terminated in 2016 .

Curium, one of two US suppliers of technetium generators, announced in January that it has converted entirely to LEU targets to produce the ⁹⁹Mo sold in North America. Curium’s targets are irradiated in Dutch, Belgian, and Polish research reactors. The Belgian BR2 reactor is one of two European neutron sources that continue to be fueled with US-origin HEU .

A spokesperson for Lantheus, the other US supplier, says that two-thirds of its ⁹⁹Mo is LEU-sourced. The other third is supplied by Belgium’s Institute for Radioelements, which uses targets fabricated from US-supplied weapons-grade HEU. That facility says it plans to convert to LEU operations by 2020.

Avoiding HEU-based processes has been further incentivized by the Centers for Medicare and Medicaid Services, which provides an extra payment for ^99mTc doses that are derived from LEU.