Isotope shortage strains hospitals

The abrupt shutdown of two aging nuclear reactors that produce a radioisotope widely used in medical imaging has forced physicians in the U.S. and abroad into a crisis, requiring them to postpone or cancel necessary scans for heart disease and cancer, or turn to alternative tests that are not as accurate, take longer and expose patients to higher doses of radiation.

Because of limits on testing produced by the shortage, some patients will undergo heart or cancer surgeries that could have been prevented by imaging, and others will miss needed surgeries because of the lack of testing, said Dr. Michael Graham of the University of Iowa, president of SNM, formerly the Society of Nuclear Medicine. “It’s possible that some deaths could occur,” he said.

Private companies and government agencies in the U.S. and Canada are looking at new sources of the radioisotope, including the possibility of building new reactors and modifying existing research reactors, but any long-term solution is at least two to three years in the future, experts agree.

The situation is complicated by efforts by the U.S. government, the sole provider of the uranium used in the reactors, to shift to low-enriched uranium from the high-enriched fuel that is now used. Government officials fear that terrorists theoretically could divert the high-enriched form to the construction of bombs.

The shortage “is one of the greatest threats to our profession of modern times,” said radiologist Robert W. Atcher of the University of New Mexico, last year’s president of SNM.

The focus of this shortage is a short-lived radioisotope that most patients have probably never heard of -- technetium-99m, the “m” standing for metastable. With a half-life of only six hours, the isotope allows physicians to examine bones and blood flow, among other things, then quickly disappears from the body, minimizing the dose of radiation received by the patient. Because of its short half-life, the isotope cannot be stockpiled and must be used within a day or two after it is produced.

Every day of the year, nearly 55,000 Americans and tens of thousands of patients in other countries undergo nuclear medicine tests -- such as checking for the spread of cancer to the bones or monitoring the flow of blood through the heart -- most of them using technetium-99m. The radioisotope is attached to chemicals that allow it to bind to specific sites in the body, where it emits gamma rays that can be used to produce an image of the area.

The technetium-99m used in these tests is produced in five reactors around the world, all of them at least 45 years old and none of them in the United States.

Three times within the last 18 months, the National Research Universal reactor in Chalk River, Canada, which normally supplies about a third of U.S. technetium-99m demand, has shut down because of leaks of radioactive tritium-contaminated water. On May 14, it shut down for the third time, and it will not reopen until the end of the year. Some experts suspect it will never reopen if a containment vessel is badly corroded.

Even if it reopens, its long-term prospects are not good. Canadian Prime Minister Stephen Harper said this year that the country would be out of the radioisotope business by 2016 because of repeated failures to bring a new reactor online. “We can’t spend hundreds of millions of dollars and never produce an isotope,” he said.

Last month, the Petten nuclear reactor in the Netherlands, which supplies half the U.S. requirement, shut down for a month for routine maintenance and it is expected to close for at least three months next year for repairs.

Radiologists are already feeling the effects. About 91% have suffered shortages of some sort, according to SNM’s Graham.

“We have still been able to do our studies, although some scans must often be significantly delayed for several weeks due to the limited, sporadic supply of isotope,” said Dr. J. Martin Hogan, chief of diagnostic radiology and imaging services at City of Hope National Medical Center in Duarte.

“There is no question that it is delaying tests,” added Dr. Johannes Czernin, chief of nuclear medicine at UCLA’s Ronald Reagan Medical Center. “We have to reschedule patients frequently because we never know how much of the technetium we will get. . . . It is not yet at the point where it is an emergency disaster, but it makes life much more difficult.”

The shortage is also straining hospital finances.

When a shipment does come in, some hospitals are scheduling tests far into the evening and on weekends to use up the technetium before it disintegrates -- frazzling the nerves of some technicians and boosting overtime costs.

The cost of the radioisotope itself has also gone up, by at least 20% to 30%, according to Dr. Marcelo F. Di Carli, chief of nuclear medicine at Brigham and Women’s Hospital in Boston. “That’s overhead we are absorbing because reimbursement is fixed.”

With the shortage of technetium-99m, some radiologists are using fluorine-18 instead, but Medicare and insurance companies typically do not cover the cost of that test. Thallium-201 can be used for heart perfusion scans. But both alternatives are more invasive and less accurate, and can sometimes inadvertently result in large radiation doses to patients.

Supply chain

Production of technetium-99m is relatively simple -- once you get past the fact that a nuclear reactor is required. A small target made of uranium is placed inside the reactor and irradiated for five to six days. Neutrons from the reactor break down uranium atoms within the target, producing radioactive molybdenum-99, which has a half-life of 66 hours -- that is, it takes 66 hours for half of it to decay.

All five of the aging reactors use the highly enriched uranium that the U.S. is trying to phase out. A small Australian reactor using low-enriched uranium came on line this summer, but its capacity equals only about 10% of U.S. demand.

When the target is removed from the reactor, it is processed by one of the world’s three major isotope suppliers: MDS Nordion, Covidien, or Lantheus Medical Imaging. They dissolve the molybdenum in an acid solution, then bind it onto a column inside a trash-can-sized container called a technetium generator, which is delivered to radiopharmacies. The pharmacies run saline through the column to remove technetium-99m and attach it to other drugs for use in imaging.

Only two days elapse between the target’s removal from the reactor and the delivery of the technetium generator to customers.

A shutdown at any of the reactors puts a severe crimp in the delicately balanced supply chain. Shutting two is extremely difficult to overcome. Radiologists, the government and industry officials are scrambling to find ways to avert future shortages, which are expected to be even more severe.

Atomic Energy of Canada, which operates the Chalk River reactor, joined with Nordion in the late 1990s to construct two research reactors called Maple 1 and 2 to produce medical isotopes. The reactors, which cost more than $600 million total, came on line at the beginning of this decade and produced some isotopes on an experimental basis, but the reactors were mothballed last year.

The key problem was that, as the power levels were increased, the reactors tended to run faster and faster, a condition known as a positive coefficient of reactivity. That brought fears of a runaway reaction similar to that which caused the Chernobyl disaster in 1986.

Last month, Nordion called on the Canadian government to restart the reactors, which are already millions of dollars over budget. Nordion argued that computer programs now in use by the newly commissioned Australian research reactor could overcome the problems.

The Canadian government, however, has steadfastly refused to consider restarting the reactors. Even if they were restarted, the government said, it would take at least five to six years to overcome the technical hurdles and begin production.

Far-off alternatives

Perhaps the best short-term hope is the University of Missouri Research Reactor in Columbia, which could be modified to produce molybdenum-99 in two to three years at a cost of perhaps $50 million. “That is a perfect example of what we should be spending stimulus money on,” radiologist Atcher said. “It’s shovel-ready and would create jobs in the short term, as well as staffing in the long term.”

In an e-mail message, Ralph Butler, the reactor’s director, said: “We’re trying to expedite where we can, but currently, we believe it will be at least 2012 before we are able to produce [molybdenum-99] in sufficient quantities for the medical community.”

For the longer term, reactor builder Babcock & Wilcox Co. is planning to construct a reactor to produce medical isotopes, but it has not yet chosen a site and plans have not been approved by the government. Construction would probably take five to six years.

Two other companies, one in Washington and one in Winnipeg, Canada, are exploring the use of linear accelerators to shoot high-speed electrons at targets such as uranium to produce molybdenum-99. That approach would have the advantage of requiring less shielding and, unlike a reactor, an accelerator can be easily shut down in case of an emergency.

Neither company’s technology has been proven, however, and results are unlikely in the near future.

In an attempt to speed the overall efforts along, Rep. Edward J. Markey (D-Mass.) and Rep. Fred Upton (R-Mich) have introduced the American Medical Isotopes Production Act, which would provide $163 million over five years for projects including upgrading the University of Missouri reactor. The bill would also halt the export of highly enriched uranium in seven to 10 years.

But the bill cannot be considered until Congress returns from its vacation in September.

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thomas.maugh@latimes.com