BETHESDA, MD 25 June 2010—A long-standing shortage of technetium 99m (99mTc) generators has nuclear pharmacists changing their methods so that patients can receive critical imaging studies.
"We’ve done things like reducing the dosages that we’re providing for the studies, which means that oftentimes the imaging procedure takes a little bit longer," said George Hinkle, professor of pharmacy and director of nuclear pharmacy at Ohio State University Medical Center in Columbus.
In addition, he said, "we’ve shifted some of our diagnostic studies that would typically use a technetium 99 product to using another radionuclide, one that’s not in critical shortage because it’s not made by a nuclear reactor."
According to FDA, 99mTc is used in about 80% of all nuclear imaging studies done in the United States.
Until last year, nearly all of the U.S. supply of molybdenum 99, the parent nuclide of 99mTc, was produced by two nuclear reactors—one in Chalk River, Ontario, and another in Petten, the Netherlands. The rest came from other nuclear reactors outside the United States.
Atomic Energy Canada Limited (AECL) closed the Chalk River reactor in May 2009 because of a heavy water leak. According to reports from AECL, what was initially expected to be a brief shutdown lasted more than a year, with recent reports projecting a July 2010 date for resuming the production of medical isotopes.
The Petten reactor was closed for scheduled repairs this past February. Robert W. Atcher, past president of the Society of Nuclear Medicine (SNM), said during a June 7 media teleconference that the reactor is on schedule to be restarted in August.
Hinkle estimated that his nuclear pharmacy typically prepares about 150 to 180 radiopharmaceutical doses per day, about 80% of which contain 99mTc. He said his hospital felt the shortage of 99mTc generators "pretty quickly" after the Chalk River reactor shutdown, and intermittent shortages have occurred since then.
"We’ve had a couple of really difficult weeks here where we couldn’t get the molybdenum/technetium generators at all" from manufacturers, Hinkle said. "The main thing that has helped us out is the sharing that has been going on between the nuclear pharmacy here and the commercial nuclear pharmacies that are located in the Columbus, Ohio, area."
Jeffrey Norenberg, director of radio-pharmaceutical sciences at the University of New Mexico College of Pharmacy in Albuquerque and executive director of the National Association of Nuclear Pharmacies, said July is shaping up to be a "dire" month for nuclear imaging.
About 20 million nuclear medicine studies, including about 16 million that use 99mTc, are performed each year in the United States, Norenberg said. Because of supply constraints, he predicted, "probably three out of four weeks in July, none of those technetium studies may be possible."
Atcher called on the U.S. and Canadian governments to do everything possible to support the production of molybdenum 99 in both countries.
"Patients can’t afford inaction much longer. It’s time to end the medical isotope shortage," he said.
Efficiency counts. When a 99mTc generator arrives at the pharmacy, it doesn’t last long. Molybdenum 99 has a half-life of about 66 hours, and 99mTc has a half-life of about 6 hours.
FDA and SNM recommend that nuclear pharmacies schedule patients for imaging tests throughout the week, including weekends, to get the most out of each generator.
Hinkle said his institution has taken that advice, including scheduling procedures for the Memorial Day holiday, when the nuclear medicine area is not normally staffed.
"We had nuclear medicine technologists that came in to do the imaging," he said. "The nuclear pharmacy staff came in simply because we didn’t want to miss that day of radioactive materials decaying away."
Norenberg said nuclear pharmacies, in general, are working flexible hours and finding ways to stretch each 99mTc generator as far as possible.
He said that before the 99mTc generator shortage, a nuclear pharmacy might prepare a unit dose at 4:00 a.m. for 8:00 a.m. delivery to a clinic, where the material would decay until the patient arrived for a 1:00 p.m. appointment.
Now, he said, nuclear pharmacies may begin compounding later in the morning and start with a smaller dose of 99mTc that is delivered closer to patient’s the appointment time.
"It took a lot more radioactivity early in the morning to prepare that dose," Norenberg said. "By consolidating the resources and delivering just-in-time unit doses, they’ve greatly reduced the waste and the radiation exposure to the workers."
He noted that some clinics have invested in newer equipment and software to produce high-quality images with a smaller dose of 99mTc, which allows supplies to go even farther.
Other tests, more exposure. Norenberg said 99mTc has become the "gold standard" for nuclear imaging because radiopharmaceuticals made with it emit a modest amount of radiation, produce highly accurate images, and are considered very safe for patients.
"The radiation dose from radiopharmaceuticals is only a fraction of what you might get in computed tomography—CT—or an angiogram," he said. "But nonetheless, we try to keep the dose as low as reasonably achievable in order to get a diagnostic study. However, if you don’t give enough of the radiopharmaceutical to get a statistically valid sample, then you may end up having to repeat the study. That’s something we want to avoid, because that’s a potentially unnecessary radiation exposure."
According to FDA, about 60% of the tests that use 99mTc are cardiac-related procedures for which other imaging options may be acceptable. These alternatives include CT angiography, thallium 201 gamma scintigraphy, rubidium 82 or ammonia N13 positron emission tomography or CT scans, and echocardiographic or electrocardiographic stress tests.
Hinkle said these tests may not be as clinically useful as 99mTc imaging, and he worries that clinicians whose pharmacy cannot supply the radiopharmaceutical will start routinely referring patients for other imaging tests.
He remains hopeful that the 99mTc generator shortage will end this summer but uneasy about the lack of a reliable, domestic source of the radionuclide.
"There’s no long-term plan to try to correct the situation as far as the dependence that we have on outside sources for medically useful radionuclides," Hinkle said. "And there’s really nothing that can replace this particular radionuclide as far as the diagnostic imaging that’s done with it."
