Overlapping outages of several high-profile nuclear reactors are causing what the Society of Nuclear Medicine calls "one of the most significant disruptions ever" in the supply of medical isotopes.

Starting last Sunday and lasting until April 11, SNM predicts the world supply of an isotope critical to diagnosing heart disease and bone cancers will drop down to 10 or 20 percent of its normal level.

The isotope, molybdenum-99, is the parent of technetium-99, used in nearly 80 percent of all nuclear medicine and molecular imaging studies, according to SNM.

Based on the society's projections, Robert W. Atcher, Ph.D., past president of SNM and chair of their Medical Isotope Task Force, estimates that close to 20,000 patients could be forced to reschedule tests that help diagnose heart disease by measuring blood flow and that help find bone metastases.

"They'll either be delayed until there's time to have a better supply of material we need, or they'll be shifted over to another imaging procedure," he tells DOTmed News.

But while some alternatives to the blood flow exams, known as cardiac perfusion tests, or bone imaging studies exist, they have serious problems, says Dr. Atcher. They're less effective, costlier, and expose patients to more radiation, he notes. And in the case of angiography, a pinch hitter for cardiac perfusion, they're more invasive.

While some doctors have started switching to thallium-201, a potassium analogue that gives similar information about blood flow, it has performance troubles. With lower photon energy, it produces more scatter and self-absorption in overweight patients, Dr. Atcher says. And even without this problem, supplies of the isotope are still too low to satisfy the world's medical needs.

"Production for cardiac imaging has not kept up with demand for cardiac imaging. Even though producers have ramped up production for [thallium-201], we still can't meet the market," says Dr. Atcher.

Simultaneous outages

The throttling of supplies of the isotope comes from an unfortunate coincidence: a number of reactors are down at the same time, including the simultaneous outage of two of the biggest isotope-producing workhorses. The High-Flux Reactor in Petten, the Netherlands is offline, undergoing six months of repairs, and the National Research Universal Reactor in Chalk River, Ontario is also out, with an oft pushed-back restart date somewhere in May or June, at the earliest.

And though the FDA recently approved U.S. use of isotopes from the Maria reactor in Poland, one of the first new medical isotope-making reactors to enter the market in years, thanks to a deal with Covidien, no shipments have reached American shores yet. Even when they do, they won't fill the gap left by NRU: the Canadian giant was thought to account for 40 percent of the world's supply, and possessed back-up capacities allowing it to churn out larger-than-usual amounts of isotopes in the event of a crisis, such as the one the industry is facing now.

"Our estimates are that [the Maria] reactor can only produce about 5 percent of world demand. It's a help, but not an answer to the problem," Dr. Atcher says.

Still, Dr. Atcher believes it could have been much worse, and credits coordination among the world's three other main medical reactors in France, South Africa and Belgium with ensuring the crisis, though serious, is short-lived.

In fact, the Osiris reactor in Saclay, France, originally scheduled for a two-month shutdown in April, will now go under in June.

"They delayed the repairs at OSIRIS in hopes that the NRU would be back on line before the OSIRIS repairs began," writes Roy Brown, senior director of federal affairs at the Council on Radionuclides and Radiopharmaceuticals, an industry association.

Nonetheless, SNM expects future slumps in global supplies of Mo-99 to rattle the industry, with the next one coming at the end of April, beginning of May.

Lantheus, a North Billerica, Mass.-based manufacturer of radiopharmaceuticals, which along with Covidien, is one of the two main suppliers of Mo-99, says this week supplies will be "significantly lower," but hasn't determined what April's will be like.

"Clarity on available Mo-99 supply for the month of April is still being determined, although we do expect it to be consistent with our Mo-99 supply level for February and March of this year," Michael A. Wojtas, associate director of traditional products for Lantheus, writes in a letter to customers.

Chalk River troubles

Dr. Atcher hastens to note that his projections of a brief supply chain ease in mid-April don't depend on the NRU re-starting on time. As of now, Atomic Energy of Canada Limited, which runs the plant, predicts the 52-year-old reactor will be up by late spring. But with welding of the vessel to repair the site proving tricky and the AECL having to bump up restart dates over the past several months - it was originally scheduled to come online in April - Dr. Atcher isn't optimistic.

"My guess is, we'll be lucky if they're online by September 1st. That's my projection at the moment based on how slowly things are going," he says. "Each time they go into a more complicated weld, it's taken longer to achieve something that will pass muster."

And as difficult as it is, this spring's isotope dry spell is not the first. The last major moly shortage happened last August, according to Dr. Atcher, when the Petten reactor went offline for four weeks. "The advantage there was it was a fairly short period," Dr. Atcher observes.