Cyclotron technique for producing technetium-99m receives Health Canada approval

In 1971, researchers with the University of Miami published a proof-of-concept showing how a small particle accelerator known as a cyclotron could produce the world’s most commonly used medical isotope. For the next four decades, the paper sat on a shelf.

In 2009, University of British Columbia radiologist Dr. François Bénard dusted it off and thought, ‘Why not try to develop that technology?’

By then, a fragile supply chain for technetium-99m – used in medicine as a radioactive tracer – was threatening delays in diagnosing a range of deadly illnesses, including bone and cardiac diseases and cancer.

That’s because the short-lived isotope is largely a side project for a small number of aging nuclear reactors around the world whose main job is to produce electricity. As these reactors were taken offline for maintenance, the supply of technetium-99m fluctuated wildly. Plus, many reactors were approaching the end of their lifespans.

So Dr. Bénard, who is also a senior executive director of research at BC Cancer, teamed up with Dr. Paul Schaffer, associate professor at UBC’s faculty of medicine and associate laboratory director, life sciences at TRIUMF. The pair pulled together a team of scientists and explained to them how they might perfect the decades-old approach to making technetium-99m.

Dr. Schaffer remembers clearly the conference call during which Dr. Bénard proposed the project: “The chemists and nuclear chemists on the call literally paused, and then said ‘Why didn’t we think of that?’”

The team would go on to spend the next decade figuring out how to purify the isotope for medical use, scale up production and commercialize it.

Getting the green light

Late last year, the hard work paid off – their approach to making technetium-99m received Health Canada approval.

The isotope can now be produced at regional cyclotron facilities in Canada. It means dependence on nuclear reactor technology can be reduced, helping create a stable, and more environmentally friendly supply chain.

“The goal is to decentralize production and reduce the risk of making these isotopes,” says Dr. Bénard.

The reduced risk is in part because when nuclear reactors produce technetium-99m, they create a wider range of longer-lived radioactive elements than do cyclotrons. Nuclear reactors start with enriched uranium-235 and induce fission to produce radioactive molybdenum-99 (among several hundred other radioactive products). Molybdenum-99 then decays naturally into technetium-99m.

Cyclotrons, on the other hand, work by accelerating particles to very high speeds and focusing them on a target substance, triggering a reaction that produces a radioactive element. To produce technetium-99m, the team irradiated non-radioactive molybdenum-100 with protons.

Many large medical centres already have cyclotrons, which are traditionally used to make isotopes that are shorter-lived and lighter than technetium-99m – carbon, fluorine and nitrogen-based isotopes. While these isotopes are an important part of nuclear medicine, technetium-99m is even more important. It accounts for 80 per cent of all nuclear medicine procedures worldwide.

The BC Cancer cyclotron is the first in Canada to be retrofitted to produce technetium-99m and the team hopes there will be many more.

As Drs. Bénard and Schaffer are quick to point out, the achievement is based on a nation-wide effort, including BC Cancer, TRIUMF, UBC, Lawson Health Research Institute and the Centre for Probe Development and Commercialization.

The clinical trial, meanwhile, was conducted across multiple hospitals in Canada. Vancouver General Hospital and St. Paul’s Hospital were supplied with technetium-99m produced at BC Cancer while St. Joseph’s Health Care London and the Hamilton Health Sciences Centre were supplied from the cyclotron facility at Lawson Health Research Institute.

Beyond understanding the importance of teamwork, there is another significant lesson in the achievement, says Dr. Schaffer: “Funding basic research can yield results that can’t be anticipated. I don’t think anyone was thinking of technetium-99m when TRIUMF was built.”