Accelerators and other new facilities are producing an increasing share of the radioisotopes that were once sourced solely from a handful of research reactors around the globe; demand for alpha-emitters is increasing; and the need for an ensured supply of both radioactive and stable isotopes is now heightened as many countries seek an alternative to Russian isotopes. Those are just a few of the key points that emerged from a recent webinar, “Demand and Supply of Isotopes Around the World: From Diverse Perspectives,” organized by the World Council of Isotopes, along with the Sylvia Fedoruk Canadian Centre for Nuclear Innovation and the University of Saskatchewan, the hosts of the upcoming 11th International Conference on Isotopes (11ICI).
The conference organizers recently decided to postpone 11ICI, which will now be held July 23–27, 2023, in Saskatoon, Saskatchewan, Canada. The April 28 webinar on isotope supply and demand was the first of four planned webinars being offered in the run-up to the rescheduled conference.
William Magwood, director general of the OECD Nuclear Energy Agency (NEA), moderated the discussion and provided insights based on his current role and past work leading the Department of Energy’s Office of Nuclear Energy and as a commissioner of the Nuclear Regulatory Commission. Magwood served on the NRC from 2010 to 2014, and he toured medical facilities as a commissioner during a prolonged worldwide shortage of molybdenum-99.
“I have to tell you that the discussions I had with doctors at that time still leave a very strong impression with me,” Magwood said. “The frustration, the anger that medical professionals had because of the lack of supply of molybdenum-99, which they needed to diagnose serious illnesses in their patients, was driving them to do surgeries that perhaps wouldn't have been necessary otherwise. . . . They were quite angry about the situation and to be honest I think they had a reason to be, because this was a foreseeable crisis.”
Magwood said the Mo-99 shortage revealed a systemic problem caused in part by overreliance on government facilities that produced isotopes as a sideline. Once that shortage was resolved, around 2017, “we observed that there really wasn't a present crisis, but I think that was a seed for future problems because I could see the complacency coming back. The complacency that these facilities will continue to produce the isotopes we need and that we don't have to worry about it.”
International perspectives: Magwood introduced five panelists representing isotope-producing organizations from North America, Europe, and South Africa and various sectors across the isotope supply chain, who gave brief presentations.
Amir R. Jalilian, a radioisotope and radiopharmaceutical chemist at the International Atomic Energy Agency, is leading four IAEA collaborative research projects on radioisotope and radiopharmaceutical production. Jalilian observed that while around 50 million medical procedures take place annually around the world, about 20–25 million of those procedures take place in North America, and another 10 million are conducted in European countries. Jalilian said that “a lot of efforts, especially after the challenges in around 2008, were made to use and consider other methodologies such as use of cyclotrons using proton accelerator methods as well as the recent advances in linear accelerator production of molybdenum-99.”
Jehanne Gillo, director of the DOE Isotope Program, explained that “even though we're in the Office of Science, which is a basic research effort, we’re a pseudo business. We produce and distribute radioactive and stable isotopes that are in short supply. We don't compete with industry . . . our main goal is to produce isotopes that are not produced within the United States or develop production capabilities for isotopes that no one knows how to produce.”
The DOE Isotope Program maintains a network of production sites at accelerators, reactors, and other facilities at national laboratories and universities and expects to get unique isotopes from the now operational Facility for Rare Isotope Beams at Michigan State University.
“One of our priorities, of course, is the development and provision of alpha-emitters. This is really taking the medical community by storm, and we're focusing a lot of investment and effort on making alpha-emitters available to the medical community,” Gillo said.
Ram Mullur, vice president of isotopes business at Canadian Nuclear Laboratories, is currently leading CNL’s actinium-225 initiatives on product development, facility design, and corporate development. Mullur spoke about the changing landscape for medical isotopes, including an increasing emphasis on theranostics, which he summed up as “treat what you see and see what you treat.”
“There’s a lot of excitement in these new isotopes being produced by accelerators and specialty generators,” Muller said, as he named a few such isotopes, including actinium-225, germanium-68, gallium-68, zirconium-89, iodine-124, copper-64, and linac-based copper-67. “Remarkably, the medical field is being defined by these accelerator-based new novel isotopes,” Muller added.
Renata Mikołajczak, director’s plenipotentiary for research and scientific cooperation at the Radioisotope Centre of POLATOM in Poland, explained that seven research reactors—most of which entered service decades ago—currently produce most therapeutic radionuclides in Europe: the MARIA reactor (1974) in Poland, HFR (1961) in the Netherlands, BR2 (1961) in Belgium, FRMII (2004) in Germany, the ILL reactor (1971) in France, LVR-15 (1957) in the Czech Republic, and BRR (1959) in Hungary. Mikołajczak explained the roles of three European projects: SAMIRA (Strategic Agenda for Medical Ionising Radiation Applications), TOURR (Towards Optimized Use of Research Reactors in Europe) and PRISMAP, a consortium that unifies a diverse group of medical radionuclide suppliers, researchers, and users of high-purity radionuclides.
Pieter Louw, group executive for production at NTP Radioisotopes in South Africa, explained that as a supplier of radioisotopes to markets in the southern hemisphere, South Africa doesn’t have a consortium of multiple radioisotope sources like those in Europe and United States. Louw saw demand for medical radioisotopes drop by as much as 30 percent in the initial phases of the COVID-19 pandemic, underscoring the instability of both supply and demand for medical radioisotopes.
“We don't believe it's back to the to pre-COVID numbers, but it has improved quite a bit since. On the production side we had also substantial challenges because we had to revise our entire operational model. First and foremost, we have to look after the safety of our productions . . . we were vulnerable because of staff that got infected.”
Replacing Russian supplies: Magwood began a group discussion by directly addressing the impact of Russia’s invasion of Ukraine on isotope supply. “We are all very much aware of what's happening geopolitically with the Russian supply and the fact that many countries are no longer going to import Russian materials, particularly stable isotopes, but some of these stable isotopes are extremely important as precursors to production of, for example, lutetium-177,” Magwood said.
Gillo responded, explaining that the DOE Isotope Program has a reserve of 240 stable isotopes and plans to have a modern calutron facility phased in and completed by the end of the decade. She added that the facility is “not phasing in as quickly as I would like. We are definitely funding limited, and I do worry about shortfalls. I think everybody recognizes that there are already some shortfalls with things like ytterbium-176 [which is used as a feedstock for lutetium-177], that’s something that we're quickly ramping up. But there are already shortfalls in stable isotopes, so I think we can expect more in the next few years as we move to increase our capabilities.”
Full-cost recovery: Magwood asked every panelist whether their programs were selling isotopes at a price that allowed full-cost recovery—including a proportionate share of overhead costs such as maintenance and waste management at the facilities that produce the isotopes. Full-cost recovery pricing could help stabilize the market for radioisotopes and encourage investment from commercial suppliers.
While the panelists all agreed in principle with the value of full-cost recovery, many international programs are still working toward that goal.
Speaking for the DOE Isotope Program, Gillo said, “All of the commercial radioisotopes that we sell are at full-cost recovery. Research isotopes we provide at a slightly reduced cost price in order to promote their use. But for stable isotopes right now, we're finding it is very difficult for us to develop new capabilities and to sell those isotopes at full-cost recovery to start, because it's very difficult bringing all of these new capabilities online. It will take us some time before we can actually have large enough capabilities to realize the cost effectiveness and be able to sell stable isotopes at full-cost recovery.”
She continued, “Dependencies on some countries occur because they can produce them very cheaply, and perhaps provide them at not full-cost recovery, and so you then get dependencies, single-source dependencies on a particular country, which makes it very challenging . . . in this particular climate. But we're poised to step in and fill gaps, perhaps at slightly larger prices, but nonetheless we're able to fill those gaps.”