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Making Technetium-99m

Canadian scientists claim that cyclotron route to the medical-imaging isotope is the answer to shortages

by William G. Schulz
March 5, 2012 | A version of this story appeared in Volume 90, Issue 10

The key medical isotope technetium-99m can be produced directly in hospital cyclotrons, rather than by extracting the isotope from material made in nuclear reactors, a team of Canadian researchers reported on Feb. 20, at the conclusion of the American Association for the Advancement of Science’s annual meeting in Vancouver, British Columbia.

The researchers at TRIUMF, Canada’s national laboratory for particle and nuclear physics, say the method they developed will allow hospitals and clinics to make their own supplies of technetium-99m, a medical-imaging isotope that has been in short supply in recent years.

“Each year, tens of millions of medical procedures are conducted around the world with technetium-99m, an isotope used in radiopharmaceuticals for imaging disease in the heart, bones, and elsewhere in the body,” said TRIUMF’s head of nuclear medicine, Paul Schaffer. Most of the world’s supply of the isotope comes from an aging fleet of reactors, including Canada’s Chalk River reactor in Ontario, which has suffered maintenance and repair outages in recent years, threatening supplies of technetium-99m.

Until now, the reactor-based method has been the only practical way to produce technetium-99m in sufficient quantities to meet world demand and with sufficient purity of the end product. But shortages have touched off a search for alternative production methods, Leonard Mausner, a nuclear chemist at Brookhaven National Laboratory who is not affiliated with the TRIUMF research, told C&EN. Multiple efforts are under way to replace reactor-generated technetium-99m, he said, and eventually a few of them are likely to prove commercially viable.

The core of TRIUMF’s new technology to create technetium-99m involves preparing solid targets of molybdenum-100 and then bombarding them with protons generated in a cyclotron, Schaffer said. The team also developed chemistry to isolate and purify the medical isotope. “For the price of one nuclear reactor,” he added, “you can buy hundreds of cyclotrons.”

The idea of using cyclotrons to produce technetium-99m is not new, but several challenges had to be addressed to make the technology market-ready, Schaffer said. For example, he said, the team needed to be able to make the isotope in sufficient quantities and find easier ways to make the molybdenum targets.

“But our team solved every one of those challenges,” Schaffer said. Now, the team needs to seek regulatory approval in the U.S. and Canada. He said that Health Canada and the U.S. Food & Drug Administration will likely give a green light to the technology once his team shows that the end products of both production methods are “clinically indistinguishable.”

“Our team has demonstrated that the existing and growing fleet of cyclotrons in Canada—which already make isotopes for PET imaging—can be successfully used to make high-quality technetium-99m to diversify the supply of this isotope,” said TRIUMF team member François Bénard, an imaging researcher at the University of British Columbia and senior scientist at Vancouver’s BC Cancer Agency.

But Mausner told C&EN that TRIUMF’s cyclotron approach may still not be feasible in the U.S. The quantities of technetium-99m that can be produced in a cyclotron are limited, he says. And because technetium-99m has a short half-life of about six hours, there would be heavy demands on hospital cyclotrons to maintain adequate supply.

On top of that, he noted, the molybdenum targets would have to be replaced once a week or so in order to keep generating technetium-99m. With the reactor method, however, hospitals and clinics receive a solution of molybdenum-99, which decays slowly to technetium-99m. Clinicians can extract the medical-imaging isotope from this solution over and over for weeks, he says.


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