When John Nuslein began experiencing chest pain, he contacted his doctor and underwent a round of tests. But the standard electrocardiogram and cardiac treadmill were inconclusive. It took a nuclear medicine stress test — a procedure in which a radioactive substance is injected into a vein — to visualize two blocked arteries in his heart. Since then, the 66-year-old man from Albany, Oregon, has undergone multiple heart procedures.
“I would have been dead if it had not been for nuclear stress testing,” Nuslein said. “There is no question in my mind that it would have gotten a lot more severe before they found anything.”
Despite its frequent use — more than 50,000 such procedures are performed in the United States every day — the future of nuclear diagnostic testing is at risk. Most of North America’s supply of a major ingredient, a medical isotope called molybdenum-99 — or Mo-99 — comes from an aging nuclear reactor in Ontario, Canada. It is due to shut down in 2016, and proposals to replace it with other technologies have been unsuccessful.
The pending shortage poses a serious health threat, said Nick Fowler, CEO of Northwest Medical Isotopes (NWMI), a Corvallis company and Oregon State University spinoff. “There can easily be a day when someone goes into an emergency room with chest pain, and the cardiologist wants to do a scan, and there won’t be any material.”
Fortunately, nuclear engineers at Oregon State have come up with a solution. A team of a professor, two Radiation Center staff members and an undergraduate student in the Department of Nuclear Engineering and Radiation Health Physics developed a way to use low-power research reactors to generate a supply of Mo-99. Their process uses a reactor’s neutrons emanating from the core to strike an aluminum cylinder containing low-enriched uranium. The researchers have shown that neutrons interact with the uranium to create a number of different isotopes, including commercially viable amounts of Mo-99. Through a process developed by OSU, the cylinder can then be processed to remove the medically useful isotope.
Oregon State has filed to patent the technique and partnered with Samaritan Health Services and NWMI, to commercialize it. The company is proposing to contract with universities around the country and to build a centralized processing plant near the University of Missouri in Columbia. The goal, says Fowler, is to create a secure and reliable domestic supply.
As a radioactive isotope, Mo-99 decays and loses half of its activity in 66 hours. The chemical that is actually used in diagnostic tests is a decay product known as technetium-99m (Tc-99m), which lasts for an even shorter amount of time, about a day.
“This is very perishable material,” added Fowler. “Once it’s created in the reactor, we have a very short time to transport it to the processing facility, extract the moly and get it into the medical supply chain so that doctors have that technique available to them. And it has to be going all the time, 24 hours a day, 52 weeks a year.”
Dr. Matt Lindberg, a cardiac imaging specialist at Good Samaritan Regional Medical Center in Corvallis, puts it succinctly: “no isotope, no image.” Dr. Lindberg and his colleagues conduct about 1,000 diagnostic tests with Tc-99m every year. The United States is by far the largest consumer of the isotope in the world.
For more than 50 years, doctors have used such medical isotopes to visualize the body and to diagnose illnesses that now include cancer, heart disease and bone and kidney problems. Tc-99m works by emitting gamma rays that can be detected with a special camera to show blockages in arteries and areas of low blood flow. Because the isotope breaks down quickly and has a relatively low energy level compared to that of other gamma-ray emitters, it poses a minimal health risk.
When he first heard of the need for a new supply of Mo-99, Steve Reese, director of the Oregon State Radiation Center, was skeptical that university reactors could play a role. “When I was first asked if there’s a way to do this, I said ‘no.’ Because of the way the process traditionally worked, you really couldn’t use small reactors like the one we have here at OSU,” he said.
But Reese decided to take a closer look at the problem and worked with Oregon State colleagues Todd Palmer, Todd Keller and Madicken Munk, an OSU undergraduate from Coon Rapids, Minnesota. “We checked hundreds of possibilities to see what this could look like,” said Reese. “And we came down to one geometry (shape) and one vision.” The Oregon State Research Office filed for a patent, which includes Munk, who graduated from OSU and is pursuing a Ph.D. in nuclear engineering at the University of California, Berkeley.
To develop the isotope technology, Oregon State and NWMI received support from the Oregon Nanoscience and Microtechnologies Institute (ONAMI), said Fowler. ONAMI provided funds to study techniques to create Mo-99 in the Oregon State research reactor. Fowler called ONAMI’s support “critical to our process.”
NWMI has filed a Notification of Intent to make a formal application to the U.S. Nuclear Regulatory Commission for permits to build the processing plant in Missouri. The company expects to break ground on that facility in 2015 and to begin production of Mo-99 in 2016.
Meanwhile, research on the procedure for generating and processing Mo-99 continues at the Oregon State Radiation Center. “This will save lives and help us to attract students and research faculty,” said Reese.