FDOPA PET brain scan. Source: Hôpital Neurologique Pierre Wertheimer, Bron, France

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

Each day more than 50,000 patients in the U.S. undergo diagnostic and therapeutic procedures using medical isotopes, and eight out of every 10 of these procedures require Tc-99m, which also is used in 80 percent of imaging scans performed in Europe. The molecular imaging community survived the Mo-99 shortage through various strategies, but it needs to continue to employ these survival strategies and develop new ones as the supply is likely to remain precarious as the Canadian and Dutch reactors are de-commissioned.

Survival strategy #1: Lower the dose

Among the lessons learned during the Mo-99 shortage is the fact that it is possible to maintain excellent image quality using low dose imaging protocols. Many physicians intend to continue low dose protocols beyond the current shortage. The strategy carries a double benefit, 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. It mitigates the impact of the shortage and minimizes radiation exposure to patients.

SNM is collaborating with the American Society of Nuclear Cardiology (ASNC) to develop guidelines that recognize the decreased doses of technetium, adds Michael M. Graham, MD, PhD, immediate past-president of SNM and professor of radiology, University of Iowa in Iowa City.

Cardiac imaging, which accounts for 50 percent of nuclear medicine imaging studies in the U.S., has displayed a fair amount of ingenuity, says Robert W. Atcher, PhD, MBA, director of the National Isotope Development Center, 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 [normal],” Atcher explains. This protocol halves the amount of Tc-99m needed. Because Tc-99m sestamibi redistributes, comparison of five- and 60-minute stress images using FHRWW [Fleming Harrington Redistribution Washin Washout] allows the physician to detect ischemia, suggests Richard M. Fleming, MD, a nuclear cardiologist at the Cardiovascular Institute of Southern Missouri in Poplar Bluffs, Missouri, and at the Sierra Nevada Cardiology Associates in Reno, Nev. “Stress imaging after a single dose of Tc-99m sestamibi is superior for ischemic detection,” he says.

High-speed SPECT gamma cameras offer another arrow in the quiver. They acquire images much faster and potentially allow physicians to further reduce the amount of isotope used, adds Fleming.

Survival Strategy #2: Identify alternate isotopes

The nuclear medicine community has resorted to a common tactic used in shortages; they’ve substituted alternate resources. Specifically, they’ve rediscovered thallium-201 for cardiac imaging. Lantheus Medical Imaging increased its thallium production by almost 300 percent during the shortage and could not meet the needs of the market, notes Atcher.

However, there are downsides with thallium imaging. It is less useful in obese patients because it is a lower energy photon than Tc-99m, he says. “We are falling back on a decade’s worth of improvements by going to thallium from technetium,” adds Fleming.

Rohren’s group at MD Anderson Cancer Center reassessed many other imaging studies, including bone scans, MUGA (MUltiple Gated Acquisition) cardiac scans, and parathyroid scans, which use Tc-99m as their primary radiotracer during the crisis. The group plans to use nitrogen-13 ammonia for PET cardiac imaging and FDG for cardiac viability, and has used 18F-sodium fluoride (NaF) PET imaging for bone scans during times of severe shortage.

An ongoing challenge

“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 … We are not clear where the capacity is ultimately going to come from,” says Alexander J. McEwan, MD, professor and division director, division of oncologic imaging, department of oncology at University of Alberta, Edmonton, Canada. The ultimate solution hinges on a combination of initiatives working in tandem.

On the international front:

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

However, identifying reactors throughout the world for Mo-99 production cannot guarantee the medical isotope supply in the U.S. When the volcano in Iceland erupted in April, the shipment from Europe was stopped. “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 again put us in a very precarious position relative to being able to do nuclear medicine in the U.S.,” says Atcher.

“Nationally there are at least three initiatives that are slowly moving forward but would benefit immensely from better funding and particularly from Representative Edward Markey’s (D-Mass.) American Isotope production bill,” says Graham. The three possibilities are the University of Missouri reactor, the GE/Hitachi collaboration and the Babcock & Wilcox/Covidien collaboration. The isotope bill would authorize the appropriation of $163 million to support initiatives to produce Mo-99, which could significantly reduce the time to complete the proposed projects. It is currently held up in the Senate by Senator Christopher S. Bond, (R-Mo.).

At the ready

The current crisis is mitigated but can certainly flare up at any time. As policymakers around the globe strive to develop proactive plans, imaging facilities also require backup plans should the shortage re-emerge. In the future, lessons learned from the Moly crisis of 2010 could avert a repeat of the crisis. Specifically, the combination of international cooperation and strategic conservation could establish a more secure supply of Tc-99m.