The quiet world of nuclear medicine is about to get a lot quieter -- not for lack of work, but because of a looming shortage of radioisotopes.
Much of nuclear medicine depends on a steady supply of an isotope called molybdenum-99, a byproduct of nuclear fission. The molybdenum is packed into so-called "generators" and, over about a two-week period, each generator delivers a supply of another radioactive substance, technetium-99m.
The technetium-99m is used in more than 16 million nuclear imaging procedures every year in the U.S. alone for, among other things, sentinel node biopsies in cancer surgery, bone scans, and staging cancer patients.
But the main source of supply for North America -- the NRU reactor in Chalk River, Ontario -- has been shut down since last May and isn't expected back online until April at the earliest. (See Canadian Reactor Shutdown Slows Nuclear Medicine)
Meanwhile, one of the reactors that has been picking up the slack -- the Petten facility in the Netherlands -- is to shut down this week for six months of maintenance.
So far, clinicians have been "getting by," according to Robert Atcher, PhD, of the University of New Mexico, who is past president of the Society of Nuclear Medicine and chairman of its isotope committee.
But doctors aren't looking forward to the next month or so. They'll have to make do with even less, and patient care -- not badly affected so far -- will be at risk in some cases, experts said.
Reactors Too Old, Too Few
The root of the problem is the age of the machines used to make isotopes. All five reactors are 40 to 50 years old and need increasing amounts of time-consuming and costly maintenance.
The shortages also showcase a critical gap in the supply chain -- the U.S. has no domestic reactor that can make the isotopes and one is not likely to be up and running for several years.
Since last May, clinicians have rescheduled procedures as much as possible and many facilities have started using a radioactive variant of thallium, which went out of favor about 15 years ago because technetium-99m has better imaging characteristics, Atcher told 鶹ý.
But there's a limit to how much rescheduling can be done, he said. "These patients are ill -- in many cases these aren't really elective procedures," Atcher said.
While most radioisotopes are used for imaging, some are used in therapy, Atcher said. And, in a twist he said surprised him, some of those isotopes -- including iodine-131 -- are also now in short supply.
Iodine-131 is made using processes similar to those used for molybdenum/technetium, but demand is much smaller, so that experts didn't think the reactor shutdown would have a noticeable effect, he said.
But in late 2009, Atcher said, physicians were finding it hard to get their hands on the substance, which is used to treat thyroid cancer, Graves' disease, and hyperthyroidism.
"These are patients who need treatment who are now being rescheduled and delayed, because we have a shortage of the iodine," Atcher said.
Reactors in Belgium, France, and South Africa have been "rescheduling and rejuggling" production to cover the time when Petten is offline and the Canadian reactor is not yet back on line, Atcher said.
One estimate, he said, is that production will be at between 30% and 40% of normal.
"So we'll be able to squeak by," Atcher said.
That said, "there will be shortages," according to Steve Littlejohn, vice president of communications for Covidien, one of the two major suppliers of isotopes.
Since May, Littlejohn told 鶹ý, the company has been able to fill its standing orders, because the other reactors added production cycles to fill the gap left by the Canadian machine.
But it will be tough to fill those orders once the Dutch facility shuts down, he said. To add to the problem, there will be a short period in mid-March when none of the reactors will be working.
Bill Dawes, vice president for manufacturing and supply chain at Lantheus Medical Imaging, reported the same general picture -- meeting targets until now, but with a tough few weeks ahead.
"We expect the month of March will be challenging for the global community," he told 鶹ý.
How Doctors Are Coping
Clinicians have adopted a range of strategies over the past few months, trying to use the available isotopes frugally.
In Houston, institutions have tried a good neighbor policy, ensuring that all have at least some technetium-99m, according to Eric Rohren, MD, PhD, interim chief of nuclear medicine at M.D. Anderson Cancer Center.
Because of that, he told 鶹ý, "we've not had a day when we absolutely could not get isotopes."
At M.D. Anderson, he added, he and his colleagues have been decreasing by about 15% to 20% the radiation dose they use for such things as bone scans -- a measure that extends the available isotope.
The danger is, he said, "if you back off too far, eventually it's going to have an impact on image quality" and patient care.
Rohren added, "it may come to a point where we are truly facing a crisis -- I think it's more of a when, not if, to be honest."
There are alternatives for many procedures, he noted, including CT and PET scanning, using radioisotopes that aren't made in nuclear reactors. Radioactive thalium-201 and nitrogen-13 ammonia can be used for cardiac imaging. Magnetic resonance imaging can fill in some other gaps.
All of those have drawbacks -- increased cost, greater radiation burden, or lower image quality.
And for some procedures -- such as hepatobiliary scanning for suspected gall bladder disease -- there's simply no alternative. In such cases, a lack of technetium-99m "really will have an impact on patient care," he said.
On the other side of the country, "we're faring pretty well, considering," according to Allegra Bruce, a nuclear pharmacist at Boston's Massachusetts General Hospital.
The facility usually uses two technetium-99m generators a week and has been able to get just one a week for the past several months from its main supplier, filling in the gaps with occasional supply from the other company.
Because of that, she told 鶹ý, the facility is able to operate at 100% of its usual capacity two days a week and 80% on the other three days.
But unlike M.D. Anderson, she said, clinicians at her institution are still administering the full radiation dose called for in protocols. "The generators that we do have, we're working harder," he said.
And, like the Houston institution, Massachusetts General is using alternatives such as thallium in order to extend the available technetium-99m, she said.
Most of those strategies are also being employed in Chicago, according to Daniel Appelbaum, MD, director of nuclear medicine at the University of Chicago Medical Center.
But the impending Petten shutdown has Appelbaum and colleagues looking forward with trepidation. "We're certainly nervous about it," he told 鶹ý.
With the current shortage, deliveries of technetium-99m have been delayed by a day or so, and some patients could be rescheduled if necessary. But if the delays between shipments grow, he said, "suddenly you can't push things off for 24 hours."
Chicago has also tried to use other tests and modalities, he said, but as the shortages grow "there will be situations when the nuclear medicine test is really the only thing of benefit for the patients and we simply can't provide it."
It could be "a scary situation," Appelbaum said.
The nuclear medicine society and a coalition of other professional groups involved in the issue last summer urged Congress to take steps to ensure a domestic supply.
The groups argued that an existing reactor at the University of Missouri could meet half the domestic demand with little change, while a collaborative effort to build a new machine (involving Covidien and its partner Babcock & Wilcox) could supply the rest.
The U.S. Department of Energy has awarded $9 million to the latter project and GE-Hitachi has also been awarded $2.25 million to develop isotope production facilities.