Nuclear medicine radioisotopes are sourced as follows:
- 70% of nuclear medicine procedures use technetium-99m (Tc-99m) produced in nuclear research reactors.
- 20-25% of nuclear medicine procedures use radioisotopes produced in particle accelerators (mostly cyclotrons).
- 5% of nuclear medicine procedures use reactor-produced isotopes other than Tc-99m.
A large majority of Tc-99m is produced in nuclear research reactors. More precisely, the reactors produce Tc-99m’s longer-lived parent isotope molybdenum-99 (half life 66 hours) with neutron bombardment of enriched uranium targets. There is a long-established worldwide trade in Mo-99. It is supplied in the form of generators (or ‘cows’) from which Tc-99m is ‘milked’.
There are two problems:
- reliance on a relatively small number of reactors, and occasional disruptions to supply.
- WMD proliferation risks associated with research reactors, exacerbated by the frequent use of highly-enriched uranium (HEU) fuel and/or HEU irradiation targets.
There are ongoing efforts to reduce the reliance on HEU fuel and targets in reactors producing Mo-99/Tc-99m − though HEU is still used in some cases, and substituting HEU with low-enriched uranium does not entirely negate WMD proliferation risks.
A better solution would be to use non-reactor technologies (particle accelerators or spallation sources) to produce Mo-99 or Tc-99m.
Large-scale non-reactor production of Mo-99 would be ideal, as the produce could be shipped around the world. Tc-99m can be distributed locally/regionally − for example a network of cyclotrons in most of Australia’s capital cities could satisfy Australian requirements.
Below are links to literature about non-reactor methods of Mo-99/Tc-99m (and some other issues such as efforts to replce HEU with LEU).
— Electron accelerator method: Ralph G. Bennett et al., A System of Tc-99m Production Based on Distributed Electron Accelerators and Thermal Separation, Nuclear Technology, Vol.126, April 1999.
— Spallation system for Mo-99 production: Belgian Nuclear Research Centre SCK-CEN www.cen.be (type Myrrha or Adonis into SCK-CEN’s search engine).
— Aqueous homogenous nuclear reactor technology: “The aqueous homogenous nuclear reactor technology being developed by Babcock & Wilcox relies on low-enriched uranium and promises to produce only 1% of the radioactive waste that accompanies the production of Mo-99 in a conventional reactor. This week the company, a subsidiary of McDermott International (NYSE:MDR), announced receiving $9 million in funding for the alternative Mo-99 technology, which the company is developing jointly with Covidien. Adding credence to the Babcock & Wilcox effort is the award of a publicly undisclosed amount of funding to GE and Hitachi, also to develop technology capable of making Mo-99 from low-enriched uranium.” (Greg Freiherr, 27 Jan 2010, ‘Nuc med isotope supply: Perfect storm sends Covidien to cover’, http://www.diagnosticimaging.com/display/article/113619/1515968?verify=0)
— Report of the Expert Review Panel on Medical Isotope Production
Presented to the Minister of Natural Resources Canada, 30 November 2009
See esp. Chapter 5: Assessment of Options
5.1 Overarching Discussion
5.2 New Multi-Purpose Research Reactors Option
5.3 Dedicated Isotope Facility Option
5.4 Existing Reactors Option
5.5 Linear Accelerator – Photo-Fission Option
5.6 Linear Accelerator – Mo-100 Transmutation Option
5.7 Cyclotron Option
— IAEA Nuclear Energy Series, Technical Reports, No. NF-T-5.4, 2013
Non-HEU Production Technologies for Molybdenum-99 and Technetium-99m
4. REACTOR BASED PRODUCTION
5. ACCELERATOR BASED PRODUCTION
5.1. Fission based (n, f) production using accelerators
5.2. Photon based (γ, n) production using electron accelerators
5.3. Neutron induced process 100Mo(n,2n)99Mo
5.4. Direct production of 99mTc using proton accelerators
— Future Supply of Medical Radioisotopes for the UK Report 2014
Report prepared by: British Nuclear Medicine Society and Science & Technology Facilities Council.
Chapter 3: Alternative Strategies for Imaging Diagnostics in the UK
3.2 Alternative Modalities / 3.3 Use of Other Radionuclides
Chapter 4: Non-Reactor Production of Technetium-99m
4.1 Reactor Fission vs. Other Methods /
4.2 Particles and Reactions / 4.2.1 Neutron-Induced Fission / 4.2.2 Neutron Capture / 4.2.3 Photonuclear Transmutation / 4.2.4 Proton-Induced Transmutation / 4.2.5 Summary /
4.3 Particle Source Technologies / 4.3.1 Electron Accelerators / 4.3.2 Low-Energy Proton Accelerators / 4.3.3 High-Energy Protons / 4.3.4 Neutron Production / 4.3.5 Laser Acceleration
Chapter 5: Radiochemical, Pharmaceutical, Dosimetric, and Operational Considerations for Cyclotron Produced 99mTc
Chapter 8: UK Delegation to assess the viability of the Canadian schemes for cyclotron production of Na99mTc04
8.9 Conclusion: Two 99mTc production methodologies using the 100Mo(p,2n)99mTc reaction on high powered cyclotrons have been accomplished. The key innovation for the implementation of this technology resides with the target plate technology. These methods have the potential for routine production of TBq amounts of GMP product and could be established in the UK along similar lines to those using regional cyclotrons for the production of positron emitting radiopharmaceuticals. The technology represents a valuable opportunity for UK science and technology, however the reliability of routine production and backup arrangements are still to be evaluated. Further commercial investment will be requited to develop operational stability and to secure the necessary regulatory approvals before this technology is suitable for routine medical use.
— OECD/NEA (2010) Interim Report on High-Level Group on Security of Supply of Medical Radioisotopes, The Supply of Medical Radioisotopes.
— OECD/NEA. (November 2010). The Supply of Medical Radioisotopes. Review of Potential Molybdenum-99/ Technetium-99m Production Technologies.
— Gregory Morris and Robert J. Budnitz (Future Resources Associates, Inc.), 2001, “Alternatives to a 20 MW Nuclear Reactor for Australia”,
First neutron accelerator delivered to Mo-99 facility
19 October 2018
The first production accelerator has been delivered to Shine Medical Technologies’ isotope production campus in Janesville, Wisconsin. The unit will be used to gain operating experience, train employees and develop maintenance procedures at the plant, which at full capacity will be able to supply over one third of world demand for molybdenum-99 (Mo-99).
The accelerator system has been designed and built specifically for the Shine project by Phoenix LLC, also of Wisconsin, and will produce radioisotopes for use in medical imaging. Phoenix has previously designed prototypes to demonstrate the neutron output and up-time required for medical radioisotope production, but this is the first system designed for regular commercial use, Shine said yesterday.
“This delivery represents the culmination of almost a decade of joint work between Phoenix and Shine, moving from proof of concept, to proof of scale, and now to a commercial-ready unit that can produce thousands of doses of medicine per day when paired with the Shine target,” Shine CEO Greg Piefer said. The tests will prove the technology is ready for production and provide important maintenance and operational data well in advance of starting up the actual plant, he added.
Ross Radel, CEO of Phoenix, said the company’s mission is to tackle “humanity’s greatest challenges” with nuclear technology. “Through our partnership with Shine, our neutron generators will support production of enough Mo-99 to provide millions of people a year with the critical imaging procedures they need,” he said.
Mo-99 is the precursor of technetium-99m (Tc-99m), the most widely used isotope in nuclear medicine. With a half-life of only 66 hours, Mo-99 cannot be stockpiled, and security of supply is a key concern. Mo-99 has primarily been produced by a limited number of research reactors, many of which have been operating since the 1960s, and at times supply has been subject to disruptions and significant radioisotope shortages following outages at those reactors.
There has been no commercial production of the isotope in the USA since 1989. Since 2009 the US Department of Energy’s National Nuclear Security Administration (NNSA) has been working in partnership with US commercial entities to accelerate the development of technologies to produce the radioisotope domestically, without the highly-enriched uranium (HEU) targets from which most Mo-99 is currently produced. The HEU targets are themselves seen as a potential nuclear proliferation risk.
Shine’s system uses low-energy, accelerator-based neutron source to fission a low-enriched uranium target dissolved in an aqueous solution. The company in 2016 received approval from the US Nuclear Regulatory Commission to construct the facility, and announced the completion of the first building on its Jamesville campus – Building One, where the first production unit is to be installed – earlier this year.
Construction of the commercial facility, which will contain eight isotope production units each with its own Phoenix neutron generator, is to begin in next spring. Commercial production of Mo-99 is scheduled to begin in 2021.
Canada: Progress with non-reactor isotope production
A research team at the University of British Columbia is making progress developing non-reactor methods to produce technetium-99m (Tc-99m), the isotope used in around 80% of diagnostic nuclear imaging procedures. Using its Triumf cyclotron, they produced enough Tc-99m in six hours to enable about 500 scans, thereby creating a “viable alternative” to the NRU reactor which is scheduled to close in 2016.1
Clinical trials involving 50−60 patients are expected to begin this year to prove that the cyclotron-produced Tc-99m behaves in the same way as that from nuclear reactors. If the three-month trials are successful, the university says, one of Triumf’s cyclotrons “would likely be dedicated to medical isotope production”, possibly as soon as 2016.
Only a small number of research reactors around the world produce molybdenum-99 (Mo-99), the parent of Tc-99m. The supply chain has been vulnerable to interruptions from unplanned reactor outages.
The Canadian government has invested around C$60 million in projects, including Triumf, to bring non-reactor-based isotope production technologies to market through its Isotope Technology Acceleration Program initiative.
Production of Tc-99m using cyclotrons does not require the highly enriched uranium targets that are commonly used in reactors to produce Mo-99 (and Mo-99 production has sometimes been used to justify the use of highly enriched reactor fuel). Instead, technetium-99m is produced directly by bombarding a Mo-100 target with a proton beam.
Another technique that is showing some promise uses the Canadian Light Source in Saskatoon, Saskatchewan.2 The accelerator bombards a target of enriched Mo-100 with high-energy X-rays, which knock a neutron out of some of the Mo-100 atoms to produce Mo-99. If all goes to plan, two or three accelerator systems like the Canadian Light Source facility could produce enough isotopes to supply Canada’s domestic needs. Production of the parent isotope Mo-99 is preferable to direct production of Tc-99, as its longer half-life (66 hours vs. 6 hours for Tc-99m) facilitates more widespread distribution.
Numerous non-reactor methods of Mo-99/Tc-99m production have been proposed over the past few decades, and some methods have been proven on an experimental scale. There is a reasonable chance that the looming closure of the NRU reactor will result in viable, affordable methods of large-scale Mo-99/Tc-99m production.
1. WNN, 9 Jan 2015, ‘New record for cyclotron isotope production’,
2. WNN, 17 Nov 2014, ‘Canada ships first synchrotron isotopes’, www.world-nuclear-news.org/RS-Canada-ships-first-synchrotron-isotopes-1711148.html
Canada funds hunt for new isotope sources
05 March 2013
Three projects to develop new supply sources for the key medical isotope technetium-99m (Tc-99m) have been selected to receive over C$21 million ($20 million) in funding under Canada’s Isotope Technology Acceleration Program (ITAP).
ITAP was set up by the Canadian government to invest some C$25 million ($24.3 million) over four years to advance non-reactor-based technologies for Tc-99m supply and optimise the processes to help bring them to market. The three selected projects are to receive a total of C$21.45 million ($20.9 million), with the remaining C$3.55 million ($3.46 million) covering support costs for the program.
Two cyclotron projects, at the University of Alberta and the Triumf consortium in British Columbia, are to receive C$7 million ($6.8 million) each, while the Prairie Isotope Production Enterprise linear accelerator project in Manitoba will receive C$7.46 million ($7.26 million). The three projects have all shown promising results under an earlier Canadian government initiative to diversify sources of Tc-99m using cyclotron and linear accelerator technologies, the Non-reactor-based Isotope Supply Contribution Program (NISP).
According to Natural Resources Canada (NRCan), these projects have shown promising results including small-scale demonstration of Tc-99m production, but more work is required to bring the technologies to commercial-scale production and to meet regulatory requirements.
Tc-99m is the most widely used medical isotope, employed in about 80% of nuclear medicine diagnostic procedures. As the isotope itself has a very short half-life of only six hours, the longer-lived molybdenum-99 (Mo-99) is used to generate Tc-99m at the point of treatment. Mo-99 is produced in a handful of research reactors around the world: the NRU facility at Canada’s Chalk River Laboratories produces around 40% of world supply.
Mo-99 itself also has a relatively short half-life of 66 hours, so reliable, regular supplies of the isotope are essential. However, recent years have seen global shortages when several of the handful of ageing research reactors used to produce the isotope have been out of action, prompting interest in investigating alternative sources. Tc-99m can be produced directly in a cyclotron by bombarding a molybdenum-100 (Mo-100) target with a proton beam, while linear accelerators can be used to generate Mo-99 by bombarding a Mo-100 target with high-energy X-rays. Such methods are also seen as presenting non-proliferation benefits as they do not require the use of high-enriched uranium either for fuel or targets for isotope production, although LEU reactor fuels and targets are increasingly being used in reactor-based Tc-99 production.
HEU-Free Medical Isotope Project Wins U.S. Financial Support
May 9, 2012
The U.S. National Nuclear Security Administration on Tuesday said it has agreed to help fund a medical science center’s efforts to refine an accelerator-centered means for generating a key medical isotope without relying on weapon-usable uranium (see GSN, Feb. 7).
The Morgridge Institute for Research in Wisconsin is expected to expedite preparation of the system under the equal cost-sharing deal, which is valued at $20.6 million.
Molybdenum 99 through the decay process produces technetium 99m, which is employed widely in U.S. medical procedures, particularly for identifying heart ailments and cancer. The United States today cannot produce its own molybdenum 99, and international manufacturing sites in recent years have faced closures and problems that have contributed to the material’s scarcity. In addition, production at the non-U.S. sites generally depends on use of highly enriched uranium suitable for use in bombs.
The National Nuclear Security Administration has so far reached deals with four firms in the United States as part of an effort to speed up the creation of varied, dependable molybdenum resources within the nation’s borders. Non-U.S. manufacturers also receive the agency’s assistance in modifying their mechanisms to use low-enriched uranium without potential weapon applications.
“The production of this medical isotope without the use of highly enriched uranium is essential for advancing our nonproliferation commitments and minimizing the use of HEU in civilian applications worldwide,” NNSA Deputy Administrator Anne Harrington said in released remarks. “The significant technical advancement of our domestic commercial partners is critical for achieving a diverse, reliable supply of molybdenum-99 for the U.S. medical community” (U.S. National Nuclear Security Administration release, May 8).
Canadian government reports:
National nuclear medicine shortage could have a Wisconsin solution
Tom Still, August 17, 2009, http://wistechnology.com/articles/6407/
An average of 40,000 Americans per day are given a radioactive isotope that acts as a light source within their bodies, illuminating cancerous tumors and heart problems that doctors otherwise couldn’t detect – short of surgery and other procedures that are riskier, more costly and less effective.
The supply of that isotope, used widely and safely for decades, is now threatened by a shortage of the core material – Molybdenum 99 – used to produce it for hospitals and clinics. It’s an emerging crisis with national and even international dimensions, yet a dilemma that could be solved by a Wisconsin company called Phoenix Nuclear Labs.
Scientists working with the Madison-based company believe they can generate the neutrons necessary to create Mo-99, an essential nuclear medicine tool, without using a nuclear reactor to do so. It’s a safer and more sustainable method than the status quo, which relies on production of Mo-99 from five retirement-age nuclear medicine reactors – two of which are now shut down, one perhaps permanently.
The idled reactors in Canada and the Netherlands supply 92 percent of all Mo-99 used in the United States, where some 25 million doses are given each year. Eighty percent of nuclear medicine scans use the isotope, called Technetium-99 after refined for clinical use, to detect cancer, heart disease or kidney illness.
The isotope allows physicians to examine bones and blood flow, among other things, then disappears within hours from the body, minimizing the dose of radiation received by the patient. Because of its short half-life, the Mo-99 isotope cannot be stockpiled and must be used within a week after it is produced.
Already, nuclear medicine doctors and pharmacists nationwide are reporting widespread shortages, with thousands of procedures delayed each day. While they can handle part of the caseload in other ways, doctors say it’s only a matter of time before more patients miss necessary scans – or pay much more to get them.
“It’s possible some deaths could occur,” Dr. Michael Graham of the University of Iowa, president of the nation’s largest nuclear medicine association, told the Los Angeles Times.
Enter Phoenix Nuclear Labs, a company with ties to scientists such as Dr. Paul DeLuca, a nuclear medicine pioneer at the UW-Madison and its current provost; Dr. Thomas “Rock” Mackie, co-founder of TomoTherapy; and Dr. Harrison Schmitt, one of the last astronauts to walk on the moon in 1972 and an adjunct professor of nuclear engineering at UW-Madison. The company president is Dr. Greg Piefer, who holds a Ph.D. in nuclear engineering from the UW-Madison.
The technical details of how the company would produce Mo-99 would fill a book, but imagine a device through which electrically charged particles bombard a specific type of “plasma,” or hot, ionized gas. That produces neutrons which in turn strike a low-grade uranium solution, which produces the Mo-99. There is almost no long-lived nuclear waste, no risk of an explosive accident, and it’s about 20 times less expensive to construct than a nuclear medicine reactor – if one could be approved at all.
The process may also benefit national security: The Phoenix Nuclear process could be operated at home or abroad without fear of the waste being reused to make atomic weapons. That’s not true of the current isotope production process, which some observers believe is vulnerable to nuclear terrorism.
The security angle is one reason why Piefer and Phoenix Nuclear were selected to present at the third annual “Resource Rendezvous,” a conference that attracts federal science and technology experts to review Wisconsin technologies and companies. The conference, organized by the Wisconsin Security Research Consortium, will be held Wednesday at UW-Milwaukee.
“This system offers a near-term solution for a very real problem that is affecting patients today,” Piefer said. “The core technology has been demonstrated over decades. Now, we’re putting it to use to improve nuclear medicine. Over time, there will be energy and security applications, as well.”
As the isotope shortage gains national attention, look for a Wisconsin company to be a part of the solution.
General Electric Abandons Plan for HEU-Free Medical Isotope Production
Feb. 7, 2012
Business considerations have prompted General Electric not to move forward with a system it devised in 2010 to produce a key medical isotope without weapon-usable highly enriched uranium, the New York Times reported on Monday (see GSN, Nov. 2, 2011).
Molybdenum 99 through the decay process produces technetium 99m, which is employed widely in U.S. medical procedures, particularly for identifying heart ailments and cancer. The Chalk River nuclear site in Canada now produces the bulk of the material used in North America, but that site is due in four years to lose its operating permit. Safety concerns prompted the Canadian site’s temporary closure in 2009, and maintenance requirements prompted a Dutch production site to suspend operations at roughly the same time.
The U.S. Energy Department has sought a means to produce Molybdenum 99 without bomb-capable material or potentially dangerous atomic systems.
General Electric vetted its new manufacturing method in test reactors and selected the Clinton Power Station in Illinois to stage the process on a larger scale. The company established plans to outsource components of the operation to various enterprises, including the Atlanta-headquartered firm Perma-Fix, which had developed a material to increase the efficiency of the technetium 99m conversion process.
The Chalk River site’s reopening, though, prompted General Electric to reassess the viability of its business model. The company said it and the Illinois plant’s operator believe “large quantities of molybdenum 99 could safely be produced” with the new method, but calculations “do not support the remaining cost.”
“We’ve put all the engineering aside” for the time being, though changing business conditions could prompt General Electric to again pick up the project, said Kevin Walsh, renewable energy head for GE Energy Financial Services.
The establishment of a new molybdenum 99 production method could be impossible as long as some facilities continue to create the material with bomb-grade uranium, according to specialists.
“The economics is key,” said Parrish Staples, who heads European and African threat reduction for the Energy Department’s semiautonomous National Nuclear Security Administration.
Staples has held talks with European government representatives in an effort to end use of weapon-capable material in the isotope production process. The old manufacturing sites receive state funding, he said.
Separately, NorthStar Medical Radioisotopes of Wisconsin and the firm Babcock and Wilcox have also received NNSA backing for their own processes for generating Molybdenum 99 without highly enriched uranium (Matthew Wald, New York Times, Feb. 6).
Faster, safer medical isotopes
U of W pins hopes on linear accelerator
Hilary Roberts, 03/3/2012
Researchers at the University of Winnipeg are preparing to commercialize a new manufacturing process for producing medical isotopes that doesn’t use uranium — and doesn’t produce radioactive waste.
It’s a breakthrough that could have significant medical benefits for Canadians while producing millions of dollars of profits a year for the university.
Instead of using a nuclear reactor to produce the isotopes, researchers found a machine called a linear accelerator can produce the isotopes needed for many medical diagnostic tests without yielding any radioactive waste, said project co-leader Prof. Jeff Martin, a U of W physicist.
“You switch them off and they’re off,” he said. “You can walk right in (to the room). There’s no residual activity around.”
A medical isotope is a radioactive substance injected into a patient’s body to help diagnose a range of illnesses, Martin said. Doctors then use a camera that detects radiation to find the problem.
Martin and his team used a linear accelerator to produce these isotopes, a device that “takes electrons and pushes them to high speeds using radio waves,” Martin explained. For this project, the electrons come out the other end and hit a target, a metal called molybdenum-100.
“We fire (the electrons) into molybdenum and initiate nuclear reactions that change molybdenum-100 into molybdenum-99,” Martin said. “Molybdenum-99 actually itself decays into technetium-99m, and that’s the real isotope that everybody uses for imaging.”
One such accelerator can be found in Pinawa, about 114 kilometres northeast of Winnipeg, but it’s not powerful enough to produce medical isotopes, Martin said. He and other researchers travelled to Ottawa to test the process on a faster accelerator.
“We think that with one accelerator running at the University of Winnipeg or in Pinawa, we would have certainly enough to do the province of Manitoba and probably more than that,” said Martin, who believes three accelerators would be enough to meet the demand for medical isotopes across Canada.
In 2009, a temporary halt in the production of medical isotopes at the nuclear reactor in Chalk River, Ont., caused an isotope shortage.
The Chalk River reactor may be shut down in 2016, but even if it isn’t, Canada may no longer have access to the United States’ stockpile of highly enriched uranium, which is used in nuclear reactors to produce medical isotopes, Martin said.
In 2011, the federal government, searching for a safer, non-reactor-based source of medical isotopes, gave funding to four projects across Canada.
U of W researchers joined with the Winnipeg Regional Health Authority and Acsion Industries to form a company named the Prairie Isotope Production Enterprise (PIPE) for this project. PIPE received $4 million from the federal government to do its research.
Unlike the medical isotopes made with cyclotrons, isotopes made with linear accelerators don’t produce any nuclear waste but do last longer, making them safer and more easily transportable, Martin said.
For PIPE to reach its goal of commercial production by the fall, the group will need to purchase a linear accelerator, at a cost of $6 million, or upgrade the accelerator in Pinawa, which would cost $2 million, Martin said.
The group wants to meet with provincial officials next week to ask for funding to set up a suitable linear accelerator in the province, he said.
Production of isotopes could make $2.5 million to $3 million per year from one linear accelerator if sales of the isotopes are expanded beyond just the Winnipeg market, said Jeremy Read, a U of W senior executive officer.
PIPE is also looking to manufacture and sell systems that would allow hospitals and other groups to produce their own linear accelerator-produced medical isotopes, Martin said.
Radioactive medicine can be made without nuclear reactors, scientists show
February 20, 2012
By Margaret Munro, Postmedia News
Canadian scientists have shown they can make radioactive medicine without the headache of using aged nuclear reactors.
The new process, which could go a long way toward solving the world’s shortage of medical isotopes, uses hospital cyclotrons to make the compounds and bypasses the need for reactors.
“It’s essentially a win-win scenario for health care,” Dr. Francois Benard of the BC Cancer Agency told a news conference Monday at the annual meeting of the American Association for the Advancement of Science. “We have found a practical, simple solution that can use existing infrastructure.”
The team, led by the TRIUMF nuclear lab based at the University of B.C., has produced technetium-99m in cyclotrons in Ontario and B.C. The scientists describe it as a “major milestone” in the international race to come up with new ways to make the critically important isotope.
Technetium-99m is used to help detect cancers, blocked arteries and heart disease in millions of people around the world each year. The supply is, however, often disrupted because 75 per cent of the technetium-99m is now made at the trouble-prone Chalk River reactor near Ottawa and another aging reactor in the Netherlands.
Canada, which pioneered nuclear medicine, is seen as largely responsible for the precarious state of the global supply. New MAPLE reactors built at Chalk River were to supply the world with medical isotopes, but were mothballed, at a cost of over $500 million to Canadian taxpayers, because of technical flaws.
Several countries are now looking for new ways to make the isotope, and the Harper government last year handed the country’s nuclear medicine whizzes $35 million. It challenged them to produce the isotope without using a reactor or weapons-grade uranium, which is now imported from the U.S. to make isotopes in the Chalk River reactor.
“It’s a friendly competition,” Benard said of the competing Canadian teams.
One of the big advantages of his team’s approach is that they can use existing cyclotrons — there are 12 across Canada — regardless of brand or type of machine.
“The goal was to develop a technical solution that would work for many people, not just one machine or one brand of machine,” said Benard.
Cyclotrons are essentially large electromagnets that accelerate streams of charged particles to incredibly high speed.
The technetium-99m was made in the cyclotrons from molybdenum-100, a naturally occurring compound mined in many parts of the world. Small discs of molybdenum-100 were strategically placed in the cyclotrons and the beams of energy stripped off subatomic particles, transforming the molybdenum-100 into technetium-99m.
It has been known since 1971 that it was possible in principle, but the idea was shelved. “A lot of people were saying this cannot be done, there were too many obstacles,” said Benard.
Paul Schaffer, head of TRIUMF’s nuclear medicine division, said it was quite a technical challenge. The team had to figure out how to package molybdenum-100 to withstand the intense irradiation and devise a way to automatically extract the radioactive disc and move it so it could be clinically processed.
The researchers don’t see scaling up production as a problem.
“One of these cyclotrons can supply a metro area such as Vancouver and there are more than a dozen of these cyclotrons in hospitals across Canada,” said Tom Ruth, a senior scientist at both TRIUMF and the BC Cancer Agency and the team’s principal investigator.
Discussions are underway with several industrial partners and regional health authorities about ramping up isotope production, said Ruth. “The science and the technology are essentially ready.”
The technetium-99m from the cyclotrons appears to be identical to isotopes made from enriched uranium in nuclear reactors, Benard said, but he expects Health Canada will require clinical trials. The trials could start within a few months, he said, and commercial production could begin in a few years.
He said Canada might need a few new cyclotrons if the technique is embraced in a big way. Cyclotrons are not cheap, at $1.5 to $3 million a piece. “But that’s a far cry from the $1-billion price tag of a new nuclear reactor,” Benard said.
Funding for Canadian isotope-producing accelerator
29 June 2010
A new advanced electron linear accelerator facility that will be able to produce medical isotopes will go ahead with the announcement of funding from the government of British Columbia.
The C$62.9 million ($60 million) Advanced Rare Isotope Laboratory, given the acronym Ariel, will be built at the Triumf subatomic physics laboratory in Vancouver. It will feature an underground beam tunnel surrounding a state-of-the-art electron linear accelerator (e-linac) capable of producing what Triumf describes as one of the most powerful beams in the world, with up to 500 kW of electron beam power. Ariel will use an e-linac that relies on superconducting radiofrequency technology to accelerate particles close to the speed of light and will provide Canada with a facility that will be at the forefront of particle and nuclear physics, according to British Columbia premier Gordon Campbell.
Construction work on the facility is due to get under way in July 2010, with the e-linac due to be installed in 2013. The facility will be commissioned for isotope production in 2014 with routine ’round the clock’ operation by 2015, according to Triumf, which is a joint venture of Canadian universities supported in its operations by the national government and in its building infrastructure by the provincial government of British Columbia.
Most of the world’s medical isotopes are currently supplied by nuclear research reactors. Over recent years, routine and unexpected outages at the world’s increasingly ageing isotope production reactors have put increasing pressure on medical supplies. Isotope suppliers have worked together to minimise the impact, and moves are under way to build new production capacity at Petten in the Netherlands.
Meanwhile, others are looking into ways of producing radioisotopes in ways that do not rely on research reactors and highly enriched uranium fuel. The Canadian government recently announced plans for a major project to promote non-reactor based routes to manufacture medical isotopes. Ariel will have a major role in producing medical isotopes, as well as producing exotic isotopes for a range of research and development purposes.
Linear accelerators are routinely used for a raft of research applications, but can also be used to produce radioisotopes. Ariel will do this by firing a beam of high-energy electrons onto converter material which in turn produces an intense proton beam. These protons are then directed onto a target of a material such as beryllium or uranium. The protons shatter the nuclei of the atoms in the target material, producing a range of radioisotopes that can be collected and separated.
University of Victoria president David Turpin said expressed excitement about the ‘tremendous potential’ of the project. “This facility will have a dramatic impact in multiple sectors of research, the health sciences and commercialization,” he said.
The lion’s share of the funding for the new facility is to come from a C$30.7 million ($29.2 million) investment from the provincial government, with Triumf and its partners providing C$14.4 million ($13.7 million) and the Canada Foundation for Innovation providing C$17.8 million ($17 million).
Federal Government Funds Technology for Medical Isotopes
March 29, 2010
The Government of Canada, through Western Economic Diversification Canada, has committed $3 million to the University of Alberta (U of A) to explore the testing and validation of processes and technologies by which medical isotopes can be manufactured and used by the health care community for medical and diagnostic purposes.
This investment in technology commercialization will allow Canada’s best and brightest to get their products to market, and promote new approaches to isotope production,” said the Honourable Lynne Yelich, Minister of State for Western Economic Diversification.
The Government of Canada is investing in the University of Alberta’s purchase and installation of a 24MeV Cyclotron. Through the use of this equipment, the U of A will map out and patent new medical isotopes production processes and technologies using particle accelerators.
’s investment in Canadian technology will enable the University of Alberta to develop and commercialize new methods of manufacturing diagnostic medical isotopes,” said Dr. Sandy McEwan, Chair and Professor, Department of Oncology, Faculty of Medicine and Dentistry, the University of Alberta. “
This cyclotron, located at the U of A will attract new researchers to the Province, build knowledge capacity and lead to new training opportunities for scientists, technicians and technologists.”
The investment at the University of Alberta represents an opportunity to contribute to commercializing new processes and products in isotope production. To capitalize on this opportunity, the U of A will validate the development of a business model utilizing a cyclotron-based isotope production platform. This project will map out and patent medical isotope production processes and technologies and introduce them to the global marketplace. This model proposes to demonstrate the direct production of isotopes utilizing cyclotron technology manufactured by Advanced Cyclotron Systems Inc (ACSI), based in Richmond, British Columbia.
This initiative will contribute to strengthening the western Canadian innovation system, and more specifically, aligns with WD’s priority to support knowledge-driven and value-added economic activities, and build on both traditional and emerging industries to create a more diversified and resilient economy in Western Canada.
Western Economic Diversification Canada works with the provinces, industry associations and communities to promote the development and diversification of the western economy, coordinates federal economic activities in the West and represents the interests of western Canadians in national decision making.
Dr Adrian Paterson, CEO of ANSTO (Australian Nuclear Science and Technology Organisation)
Senate Economics Legislation Committee
Monday, 1 June 2009
Dr Paterson—We have very carefully followed the development of non-reactor techniques. In fact, there has been a recent series of discussions in the public domain about this. We are also tracking it through a number of bilateral interactions and discussions. At the management breakaway last week, we have decided to put together an internal paper on this so that we can understand the short-, medium- and long-term implications of the potential for developing moly-99 by alternative routes. It is just a prudent practice to know what is happening and to have a good insight into it. My belief is that we will probably, within the seven to 10 year time frame, see the first attempts to produce moly-99 on a reasonable economic basis using accelerator based techniques. My view is that the cost will be very high initially and it is unclear how long the learning curve will be. But, we are certainly well aware of these developments, we track them actively and we all understand them deeply.
MEDICAL ISOTOPE PRODUCTION WITHOUT HIGHLY ENRICHED URANIUM
Committee on Medical Isotope Production Without Highly Enriched Uranium
Nuclear and Radiation Studies Board
Division of Earth and Life Studies
NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Partnership aims to meet US radioisotope needs
12 May 2009
Shortages of medical radioisotope molybdenum-99 could be a thing of the past in the USA according to an academic-industrial partnership that claims its novel manufacturing method will meet all the country’s needs.
Positron Systems Inc and Idaho State University’s (ISU) Idaho Accelerator Center say they have developed a novel, proprietary method to produce the short-lived isotope and are currently engaged in additional research. They have now signed a letter of intent to produce and distribute Mo-99.
Mo-99 is used in medical equipment to generate technetium-99 (Tc-99), a very short-lived radioisotope with a half-life of only six hours that is widely used in diagnostic medical imaging. With a 66-hour half-life itself, Mo-99 has a shelf-life of only a few days. Supply disruptions can therefore soon have a major impact on medical provision around the world, as experienced globally in 2008 when the five research reactors producing nearly all of the world’s Mo-99, and thus Tc-99, were out of action within weeks of each other.
Now, Positron says that it has plans for a subsidiary in collaboration with the ISU Idaho Accelerator Center that will specialise in the production of commercial isotopes using particle accelerators. Positron chairman T Erik Oaas said: “Working side-by-side with ISU, we intend to replace the foreign supply of Mo-99 in the USA with a product produced here in Idaho.” Meanwhile, Pam Crowell, ISU vice president for research, said the university is on course to become a national leader in the research and development of medical radioisotopes and said the university was “excited” to be working “to help deliver vital medical products in the US.”
The Positron-ISU announcement comes days after medical isotope supplier MDS Nordiron and TRIUMF, Canada’s national laboratory for particle and nuclear physics, signed an agreement to study the feasibility of producing Mo-99 by photo fission using a linear accelerator.
Mo-99 is traditionally produced by fission of uranium in research reactors, some of which use highly enriched uranium (HEU) fuel. According to MDS Nordion, the photo fission technique not only eliminates the need to ship and handle HEU fuel, it also provides “a potential alternate solution through which to supplement the production capacity of Mo-99, and lessen the reliance on existing nuclear research reactors.”
A research group at the University of Delft in the Netherlands reported last year that it is also working on novel methods to produce Mo-99 from naturally occurring Mo-98 without the need for a high-flux research reactor.