Researchers Eye Cyclotron as Alternative for Medical Isotope Production

While John Lawrence is often referred to as the founder of nuclear medicine, it is his brother Ernest who is posthumously putting his imprint on the field.

In 1931 Ernest Lawrence invented the cyclotron - or particle accelerator - for which he was awarded a Nobel Prize in 1939. Now, after more than 80 years, the recent disruption in the supply of the world’s most widely used medical isotope has spurred researchers to look at the cyclotron as an alternative to the nuclear reactor to produce medical isotopes.

With funding from RNCan (Natural Resources Canada), TRIUMF - a leading subatomic physics laboratory in Vancouver, B.C. - and a group of collaborators is researching the viability of using existing medical cyclotrons to directly produce the medical isotope technetium 99-m without using nuclear reactors.

According to TRIUMF, these cyclotrons will be used to accelerate hydrogen ions to a prerequisite energy and then will direct them onto targets of enriched molybdenum-100 (Mo-100). As hydrogen ions are extracted from the cyclotron, the electrons are stripped off so that the beam exiting the machine is simply a stream of protons. The protons collide with the molybdenum nuclei and a certain fraction of them cause the Mo-100 to transmute into Tc-99m.

The chemical form of Tc-99m isolated using this method is identical to that obtained from the reactor-based process.

While it may seem an innovative way to find a medical isotope alternative, the feasibility of this approach has actually been known since 1971 when an article, “Production of 9m Tc on a medical cyclotron: a feasibility study,” was published by J.E. Beaver and H.B. Hupf in the Journal of Nuclear Medicine.

“So it is an old idea,” said Thomas Ruth, PhD, senior research scientist at TRIUMF. “But reactors are very efficient at producing Moly-99, which is the traditional source of technetium. People have talked about the cyclotron approach for years, but it didn’t seem competitive economically or practical in terms of the amounts you could make.”

While nuclear reactors are efficient at producing molybdenum-99, just a handful actually produce it. Canada’s National Research Universal reactor in Chalk River, Ont., supplies most of the Mo-99 used in North America, but its prolonged shut down for repairs in 2009 to 2010 demonstrated how susceptible medical facilities can be to interruptions in Mo-99 production.

The advantage of using cyclotrons, according to Ruth, is that unlike nuclear reactors, cyclotrons are already in wide use. For example, Ruth and his research team have worked on both 19 megaelectronvolt (MeV) and 16 MeV cyclotrons - the kind produced by General Electric, who, Ruth said, have been “highly interested in seeing this work.”

Canada has about 15 cyclotrons that are, or will soon be, operational and could be used to produce technetium-99m. “With Canada, you have fairly dense population centers along the border [with the U.S.] so in our model we see our major urban areas having cyclotrons that would meet the needs of those urban areas,” Ruth said. “Nuclear medicine is, for the most part, an outpatient modality, so you can have patients come to a more centralized location to get their nuclear medicine scans.”

The U.S. could be a more problematic market for the technology, Ruth said, because of its sheer size.

There have been ongoing U.S. efforts to find alternatives to nuclear reactor isotope production. For example, Babcock & Wilcox has been working on a technology involving its Aqueous Homogenous Reactor, or “solution reactor”, which would be fueled by low-enriched uranium instead of highly enriched uranium.

One of the advantages of this process would be that it wouldn’t produce the nuclear-weapons-grade waste (produced at facilities like Chalk River) that poses potential security risks, but Ruth said he believes this technology is several years away from becoming a viable source of technetium-99m.

In the end what may drive the acceptance of cyclotrons as an alternative way of producing medical isotopes will be whether it is economically viable.

“We believe the costs of the technology will be competitive,” said Ruth. “It would probably be more expensive than reactor technology, but not by orders of magnitude more expensive. And we don’t see this technology as completely replacing reactors. It’s just a piece of the puzzle.”

Ruth pointed out that like any business model, this one has to demonstrate it can turn a profit. “We haven’t been in operation long enough to understand what the true economics are,” he said. “Some of the economics involve transportation. If you are in a city, transportation won’t be a big deal, but if you trying to supply a hospital 100 miles distant, with a six-hour half life that could be a factor.”

Getting the necessary regulatory approval is another potential hurdle, but the amount of time that could take could be affected by another crisis that disrupts Mo-99 production. “Then, perhaps, the approval process could be - and you’ll excuse the pun - accelerated,” Ruth said.

From a national standpoint there is some irony that Canada “doesn’t even control its own supply of isotopes,” he said.

“It’s like what we do with our trees,” he continued. “ We cut them down and sell them offshore, and then buy them back as furniture. That’s essentially what we do with our isotopes. We make them in Canada, send them to the U.S. where they are made into generators, and then buy them. With this [cyclotron] approach, we can become masters of our own destiny in terms of our isotope supply.”

Inside the cyclotron; Photo by Gord Roy, courtesy TRIUMF