Medical Isotope Shortage Threatens Patient Care

A combination of factors must be addressed in order to solve an ongoing, worldwide medical isotope shortage, according to nuclear medicine physicians and radiation oncologists who are being forced to delay or cancel elective—and occasionally even emergency— procedures.

James Ponto, M.S., B.N.C.P. University of Iowa

Milton J. Guiberteau, M.D. University of Texas Medical School

Those factors include a virtual halt in U.S. production of medical isotopes, the aging of international reactors with no replacements planned and concerns about the use of highly enriched uranium (HEU) in light of terrorism.

"It takes a nuclear reactor to make the medical isotopes in the amounts needed," said James Ponto, M.S., B.N.C.P, a clinical professor of pharmacy and chief nuclear pharmacist at the University of Iowa Hospitals and Clinics in Iowa City. "In nuclear medicine, 80 percent of all imaging uses technetium-99m (Tc99m), which is produced from the decay of the radioisotope molybdenum 99 (Mo-99).

Nuclear medicine society SNM estimates that at least 80 percent of the nearly 20 million nuclear medicine procedures each year in the U.S. use Tc-99. The medical isotope can be labeled to a variety of substances that localize in various organs and tissues or otherwise act as tracers of biologic function. Common diagnostic imaging procedures include myocardial perfusion imaging for coronary artery disease and bone imaging to detect spread of cancer to the bones. Other procedures include evaluation of diseases of the kidney, liver and biliary system, lungs, brain and gastrointestinal tract.

Since Mo-99 decays with a half-life of 66 hours, pharmacies and hospitals can't stockpile it—once it's gone, it's gone. "A shortage is inevitable if nuclear reactors are shut down," said Ponto.

U.S. Depends on Foreign Sources

There is no reliable domestic supply of Mo-99, said Homer A. Macapinlac, M.D., a professor and chair of the Department of Nuclear Medicine at the University of Texas M.D. Anderson Cancer Center. Instead, five commercial nuclear reactors—located in Canada, The Netherlands, Belgium, France and South Africa—produce 95 percent of the world's supply.

1990 saw the closure of the last U.S. reactor producing Mo-99. Plans to build a new facility in New Mexico were dismissed due to cost concerns, with the thought that Canada could produce medical isotopes at much lower cost—in fact, two reactors had been operating at Chalk River Laboratories in Canada since 1947 and 1957. The 1947 reactor closed in 1992. The other continues to make medical isotopes today; however, the reactor was shutdown in late May due to a water leak and was not expected to be running again for a month.

In 2000, Canada built two new facilities to replace the older ones at Chalk River. Technical issues arose, however, as officials sought to fully commission the new reactors and development was halted in May 2008.

"The plan that everyone depended upon went away," said Ponto. "It's scary. It's a very fragile system."

Both the remaining Chalk River reactor and the Petten reactor in The Netherlands have been shut down several times in the past year for regular maintenance and emergency repairs.

"The reactors in Canada and The Netherlands are 40 to 50 years old, said Milton J. Guiberteau, M.D., a professor of clinical radiology at the University of Texas Medical School in Houston. Dr. Guiberteau chairs the Nuclear Medicine Subcommittee of the RSNA Scientific Program Committee. "The reactors are at the outer limits of their useful lives."

Solution Lies in Coordinating Reactor Shut Downs, Building New Facilities

The National Research Universal (NRU) reactor located at Chalk River Laboratories in Canada is among the five international commercial nuclear reactors currently producing 95 percent of the world's supply of molybdenum 99 (Mo-99). Almost all of the 16 million nuclear medicine procedures performed annually in the U.S. use technetium-99m, made from the decay of Mo-99. Nuclear medicine physicians are concerned about isotope shortages that are occurring as the NRU reactor and others experience more frequent age- and maintenance-related shutdowns. Image courtesy of the Canadian Nuclear Association.

France's Nuclear Safety Authority held a meeting in January to discuss better coordination of nuclear reactor shut downs to avoid future delays in getting medical isotopes distributed around the world. Discussion focused on synchronizing unit maintenance shut downs to allow remaining reactors to take up the slack, said Dr. Guiberteau. A follow-up meeting will be held this summer.

Beyond shutdown coordination, experts look to replace the aging reactors with new ones or convert other currently commercial reactors; however, time and cost concerns must be considered. SNM has identified the University of Missouri in Columbia and the Babcock and Wilcox commercial facility in Lynchburg, Va., as promising new sites, but construction and approval by the U.S. Nuclear Regulatory Commission (NRC) and the Food and Drug Administration (FDA) means these facilities won't be operational for at least another five to 10 years.

Mo-99 is produced by the fission of HEU. Dr. Macapinlac said the commercial site in Lynchburg wants to use lower enriched uranium (LEU), because the federal government is discouraging use of HEU for fear of terrorism. However, it is not yet clear if it is practical to use LEU for medical isotope production due to substantially lower yields, increased volume of radioactive waste and overall increased cost.

A January 2009 National Academy of Sciences report said the elimination of HEU is technically and economically feasible. While SNM leaders agreed with the long-term goal of eliminating HEU, they questioned the accuracy of the cost estimates and noted that the report failed to describe a solution to the shortage in the short-term.

Ponto said the University of Missouri reactor, which has received some funding from the Department of Energy and the State of Missouri, may be ready sooner than the five- to 10-year timeframe if all goes smoothly, but still faces many NRC and FDA obstacles. Noted Dr. Guiberteau: "We need to prepare pathways to get regulatory agency approval as quickly as possible. Both safety and speed are essential."

New Facility Will Isolate New Isotopes

Meanwhile, the U.S. Department of Energy has awarded $550 million to Michigan State University in Lansing to build the Facility for Rare Isotope Beams (FRIB). The FRIB site won't just be making medical isotopes, however—some of the facility's resources will be used for isolating new isotopes.

Sources interviewed for this story applauded RSNA, SNM and the American College of Radiology for forcing the government to take notice of the isotope shortage. "Regular and emergency procedures have been delayed almost to the point that this is a national security issue," said Ponto. "Our economic problems may cause more delays in getting new facilities built, but at least we are seeing some firm planning for the future."

"There are at least 16 million reasons why we need medical isotopes produced domestically," added Dr. Macapinlac, reiterating the number of nuclear medicine procedures performed annually that use Tc-99m.

"We must ensure patient needs are not compromised," Dr. Macapinlac continued. "This is the place for the government to place its stimulus money. The fruits of the atomic energy program continue to be harvested. We need to water this tree."