Lessons Learned from the Moly Shortage: Is the Crisis Over?

The nuclear medicine community has learned many lessons from the shortage of molybdenum-99 (⁹⁹Mo), the mother radioisotope of technetium-99m (⁹⁹mTc) during the recent shut down of both the Canadian National Research Universal (NRU) reactor in Chalk River, Ontario, and High Flux Reactor (HFR) in Petten, the Netherlands. Both these reactors are back online, but are nearing the end of their lifecycle. How are we positioned for the future?

Each day more than 50,000 patients in the U.S. receive diagnostic and therapeutic procedures using medical isotopes and eight out of every 10 procedures require ⁹⁹mTc. This radioisotope also is used in 80 percent of imaging scans performed in Europe.

New initiatives

Among the lessons learned during the ⁹⁹Mo shortage is that the fact that it is possible to maintain excellent image quality using low dose imaging protocols. Many physicians say they intend to continue this beyond the current shortage. There is a double benefit in lowering the dose—in relation to the isotope shortage and with regards to minimizing radiation exposure to patients, says Eric M. Rohren, MD, PhD, section chief of PET at the departments of nuclear medicine and diagnostic radiology, MD Anderson Cancer Center in Houston. SNM is developing guidelines in collaboration with the American Society of Nuclear Cardiology (ASNC) to recognize the decreased doses of technetium, adds Michael M. Graham, PhD, MD, immediate past-president of SNM and professor at department of radiology, University of Iowa in Iowa City, Iowa.

There has been some ingenuity applied for cardiac imaging which covers 50 percent of nuclear medicine imaging studies in the U.S., says Robert W. Atcher, PhD, MBA, past president of SNM and director of the National Isotope Development Center in the office of nuclear physics, U.S. Department of Energy and professor of pharmacy at the University of New Mexico in Albuquerque. “First, we believe we can limit imaging to a stress test. If the stress test is normal, the need for doing the rest study is pretty small. Some practices are starting to move towards not doing a rest image if the stress is small. That cuts in half the amount of ⁹⁹mTc that we need to use,” Atcher suggests.

“Stress imaging after a single dose of ⁹⁹mTc sestamibi is superior for ischemic detection,” adds Richard M. Fleming, MD, a nuclear cardiologist at the Cardiovascular Institute of Southern Missouri in Poplar Bluffs, Mo., and at Sierra Nevada Cardiology Associates in Reno, Nev. Fleming suggests that because sestamibi redistributes, comparison of five- and 60-minute stress images using FHRWW [Fleming Harrington Redistribution Washin Washout] allows the physician to detect ischemia.

Fleming adds that using high-speed SPECT gamma cameras is another possibility which will acquire the images much faster and potentially allow us to further reduce the amount of isotopes and the amount of time to do these studies. In addition, the administered activity in many other imaging studies which used ⁹⁹mTc as their primary radiotracer were reassessed, such as bone scans, MUGA (MUltiple Gated Acquisition) cardiac scans in a patient’s pre- and post-chemotherapy, and parathyroid scans, shares Rohren.

⁹⁹mTc alternatives

Physicians have rediscovered thallium-201 for cardiac imaging. Lantheus Medical Imaging increased their thallium production by almost 300 percent during the ⁹⁹mTc shortage and was still not able to meet the needs of the market, notes Atcher. But there are downsides with thallium imaging. It is less useful in obese patients because it is a lower energy photon than 99mTc, he says. “We are falling back on a decade’s worth of improvements by going to thallium from technetium,” adds Fleming.

In addition to using thallium as a backup for conventional nuclear cardiac imaging, Rohren’s group at MD Anderson Cancer Center have plans to use 13N-ammonia for PET cardiac imaging and FDG for cardiac viability, and have made use of ¹⁸F-sodium fluoride (NaF) PET imaging for bone scans during times of severe shortage. There are about four million bone scans (20 percent) done with ⁹⁹mTc every year in the U.S. But we also do not have the instrumentation to switch all these to ¹⁸F-NaF PET, adds Atcher.

The crisis is not over

Even though the Canadian NRU reactor and the Dutch HFR reactor in Petten have achieved full production again, the long-term crisis is not over, experts agree. Both these reactors are reaching the end of their lifespan—the NRU reactor started operation 53 years ago, while the HFR reactor went online 49 years ago.

“I think it is clear that NRU will close almost certainly in 2016 and there is a risk of the Petten reactor closing soon after that and we are not clear where the capacity is ultimately going to come from,” says Alexander (Sandy) J. McEwan, MD, professor and division director, division of oncologic imaging, department of oncology at University of Alberta, Edmonton, Canada.

The Canadian government has put forward a $35 million grant for alternative non-reactor-based technologies methods of ⁹⁹mTc production and the proposal results are expected in the late fall, shares McEwan. On the Dutch side, the Nuclear Research and Consultancy Group of the Netherlands is planning to build a replacement reactor, Pallas, to replace the HFR. The French Alternative Energies and Atomic Energy Commission, Belgium’s Institute for Radioelements, and Ion Beam Applications, three major distributors of radioisotopes in Europe, have recently partnered to secure the supply of ⁹⁹mTc beyond 2015.

Identifying reactors throughout the world for ⁹⁹Mo production cannot always guarantee the medical isotope supply in the U.S.  “Even though we developed additional capacities in the Polish and Czech reactors as well as the existing capability in Belgium and in France, having that shipping lane shut down because of the volcanic eruption [in Iceland in April] again put us in a very precarious position,” says Atcher.

“There is a desperate need to develop a domestic capability in the U.S. and it’s still unsolved,” says Atcher. The U.S. Department of Energy’s National Nuclear Security Administration (NNSA) had selected GE Hitachi and Babcock & Wilcox for the original round of funding in January, but neither one of them is close to being able to produce sufficient quantities to supply substantial percentage to the U.S. market, adds Atcher. The American Medical Production Act of 2009, which will allow the production of 99Mo in the U.S. isn’t yet passed and currently held up in the Senate by Senator Christopher S. “Kit” Bond, R-Missouri.

The current crisis is mitigated but can certainly flare up at any time. Imaging facilities should have backup plans ready should the shortages re-emerge. International cooperation and strategic partnership will hopefully enable us to limit the uncertainty surrounding the supply of ⁹⁹mTc in future.