Matthew Miller

mrmiller@lsj.com

The radioactive tracer known as technetium 99m is injected into more than 40,000 patients in the United States every day. It is the most important isotope in nuclear medicine, used to diagnose heart disease, trace the spread of cancer into the bones and breasts and lungs, image the functioning of the brain and spleen and liver.

And, when the Canadian nuclear reactor that produces nearly a fifth of the world's supply stops making medical isotopes two years from now, doctors won't have enough of it.

Terry Grimm thinks he can help.

In fact, Grimm, the founder and president of Niowave, Inc., a Lansing company that makes superconducting linear accelerators, hopes to one day supply much of the country's technetium 99m from a facility on Port Lansing Road across from Capital Region International Airport.

Which is not as far-fetched as it might sound.

The United States uses 50 percent of the world's medical isotopes, but those isotopes aren't produced here. They come almost exclusively from a handful of decades-old nuclear reactors in Canada and Europe.

But it's a fragile supply chain, prone to unexpected outages, and the way those reactors produce an isotope called molybdenum 99, which decays into technetium 99m, requires the American government to ship weapons-grade uranium across the globe.

So, in the wake of a long and painful shortage in 2009 and 2010, the U.S. government got serious about developing alternate sources, American sources, sources that could make molybdenum from low-enriched uranium or no uranium at all.

Which superconducting linear accelerators can. Isotope production jumped in front of other Niowave projects, Grimm said, "because it's the one that has a clear national need."

"We knew that's the market that's sitting there ready and waiting, because there is not a solution in the U.S. right now," he said.

It would be just as accurate to say that there are multiple potential solutions that haven't yet reached the marketplace, a number of companies hoping to profit from them, a host of uncertainties about the degree to which other nations with government-subsidized reactors will angle for a larger share of the $3 billion U.S. market.

Niowave broke ground last month on a $79 million isotope production facility that looks out on the runways of Capital Region International. The company expects to move in by the end of the year, to make its first medical isotopes early next year, to be producing them commercially by early 2016. It expects to add 90 jobs to its 70-member staff in the process.

"The local success in this market is going to be transformational for the region," said Jerry Hollister, Niowave's chief operating officer.

But he admits it won't be easy.

A regional power outage shut down the National Research Universal reactor at Chalk River Laboratories in Canada in May of 2009. A small heavy water leak was discovered during the shutdown and then corrosion in the reactor's containment vessel. It wouldn't go back online until August of 2010. At the time, the NRU reactor was making close to 40 percent of the world's supply of molybdenum 99.

And that wasn't the depth of the shortage. In February of 2010, corroded cooling water pipes forced the shutdown of the High Flux Reactor at Petten in the Netherlands, which supplied another 30 percent of world demand. It didn't return to operation until that September.

"There was a scramble," said Robert Atcher, who at the time was president of the Society of Nuclear Medicine and Molecular Imaging. "There was a period when were having significant problems getting enough isotope to even do emergency imaging procedures."

The shortage brought home the fragility of the medical isotope supply chain, which even now relies almost exclusively on a handful of government-subsidized reactors built during the 1960s and reaching an age in which unintended shutdowns have become more likely.

That hadn't been the plan. In the mid-1990s, Atomic Energy of Canada Ltd.began work on two reactors at Chalk River, a dedicated isotope production facility, but major technical problems led the company to abandon the project in 2008.

"Those reactors would have been able to supply the whole world," said Tom Ruth, who headed the life science group at TRIUMF, Canada's national laboratory for particle and nuclear physics, for nearly two decades. "That project put off anyone else proposing a new solution through the late '90s and early 2000s, so when the project was canceled, everyone was left flatfooted."

Adding to concerns about future shortages is the decision by Canada's Conservative government to stop medical isotope production at the NRU reactor entirely in October of 2016, which a spokesperson for Natural Resources Canada called a move toward "a market-based supply chain, without ongoing government support."

Those concerns are hardly unfounded. A report issued in April by the Nuclear Energy Agency, part of the Organisation for Economic Co-operation and Development in Paris, concluded that "current global irradiation and processing capacity is predicted to be insufficient" over the period from 2015 to 2020, "even with all producers operating ... without any unplanned or extended outages."

There will be a need for more production capacity, the report said, certainly in the short term. The vexing thing for those who might want to supply it is that, by 2020, the report says, there is likely to be "significant over-capacity."

"There are a huge number of companies that have announced they are going to build production facilities that will have capacity to provide, say, half the U.S. demand," said Chris Whipple. He is a principal with the international consulting firm Environ and chaired a National Academy of Sciences committee that met in 2007 and 2008 to assess the options for producing medical isotopes without highly enriched uranium.

If every one of them made good on those announcements, he said, "we would have three or four times more moly 99 than we need."

But they almost certainly won't. The stumbling block is that nearly all molybdenum 99 is now produced in reactors that are government owned and subsidized. While the international community is working out agreements that would set prices at a level that takes into account the full cost of production, including, for instance, the disposal of radioactive wastes, those efforts are ongoing.

Which creates the sort of uncertainly unpopular with investors, Whipple said. "No one wants to compete with Moly produced in a 50-year-old reactor that was paid for years ago."

Both General Electric and Babcock &Wilcox Co. showed an interest in the medical isotope market, but dropped those plans because of the economic uncertainty.

Which has left start-up companies such as SHINE Medical Technologies and NorthStar Medical Radioisotopes, Inc. at the head of the pack.

A dozen years ago, NorthStar licensed technologies for producing extremely pure radioisotopes, technologies that it has since applied to the extraction of technetium 99m from the less-radioactive concentrations of molybdenum produced from low-enriched uranium. The U.S. Department of Energy has contributed close to $40 million to the company's efforts.

NorthStar has a new headquarters and isotope production facility under construction in Beloit, Wisc. It has two plans for making technetium 99m, one involving linear accelerators and one that would use a research reactor at the University of Missouri, which George Messina, the company's founder and chief executive officer, says is "100 percent ready to go" once the company gets approval from the Food and Drug Administration. He expects that approval by the third quarter of next year.

Reliability of supply, quality of supply and cost are going to be important Messina said, but he also believes that "probably the biggest opportunity is to the guy who gets into the market first."

What Niowave has going for it is its machines.

The idea of using linear accelerators to make medical isotopes didn't originate with Niowave, nor did the idea that it can be done with low-enriched uranium.

"People said, 'If you can get enough electrons accelerated, you can start making useful quantities of radioisotopes," Grimm said. "We've kept an eye on it, because we've been developing these superconducting electron (linear acclerators) and their niche in the market is accelerating lots of electrons efficiently, using less electrical power than the other accelerators."

Through its work developing a free electron laser weapon for the U.S. Navy, Niowave has made accelerators that are compact, robust and powerful. And where a standard linear accelerator can be run only intermittently, a superconducting accelerator could run 24 hours a day.

"It's always on," Hollister said. "The power coming out the back end, everything else being equal, is 100 times greater, so that gives us a huge advantage."

The company has just begun a collaboration with National Nuclear Security Administration, which will provide technical expertise to the project. It has begun the process of applying for a license to produce molybdenum from the Nuclear Regulatory Commission.

"It's true that, if all of these different groups make progress that there's going to be more supply than there is demand," Hollister said. It's true that it would difficult as as a private company to compete against subsidized reactors. It's true that the market is competitive.

"That's why it's going to take a concerted effort from every interested party for our project to succeed," he said.

About Niowave, Inc.

Niowave is in the business of building superconducting linear accelerators and their components. It's goal is to bring to market technologies developed over the last few decades at the country's national laboratories and at places such as Michigan State University's National Superconducting Cyclotron Laboratory, where the company's founder Terry Grimm once worked as a senior physicist.

Grimm and a group of private investors started Niowave in 2005. They moved the company into the former Walnut Street School building in north Lansing in 2006, added a research facility to the property in 2012 and broke ground on a $79 million isotope production facility near Capital Region International Airport last month.

The company employs 70 people and expects to add 90 as operations ramp up at the isotope production facility over the next few years.

Niowave counts several U.S. Department of Energy national laboratories among its clients, along with national labs in the United Kingdom, Germany and France. It manufactured three competing designs for an upgrade to the Large Hadron Collider at CERN in Switzerland.

What's next

Niowave, Inc. expects construction on its $79 million isotope production facility near Captial Region International Airport to finish by the end of the year. The maker of superconducting linear accelerators expects to produce its first isotopes early in 2015 and to ramp up to commercial production by early 2016.

Technetium 99m

Technetium 99m is a radioactive tracer used in more than two-thirds of nuclear medicine procedures, some 15 million a year in the United States alone. It is popular, in part, because it has a half-life of just 6 hours and exposes patients to less radiation than other radioisotopes.

Technetium 99m is used to trace the flow of blood and diagnose of heart conditions. It use used to trace the spread of cancers into the bones, breasts, lungs and other parts of body. It is used for functional imaging of the brain and spleen and any number of other organs.