Science 1663

The Life-Saving Business of Radioisotopes

Every month, Los Alamos produces enough radioactive strontium-82 to permit an estimated 6,000 heart diagnoses via PET scans.

Some 40 feet beneath the mesa top that rims Los Alamos canyon, in a heavily shielded room appropriately dubbed "the cave," atoms are being transformed. Energetic protons from an accelerator are sent smashing through a series of targets. When a proton slams into the nucleus of one of the target's constituent atoms, it transforms that ordinary, stable bit of matter into something extraordinary: a radioactive nucleus made specifically to serve society.

Radioactive nuclei, also called radioisotopes (or radioactive isotopes), emit energetic particles and/or gamma rays as they decay and become other nuclei. These radiations, while potentially dangerous, nonetheless make radioisotopes uniquely useful.

For example, home smoke detectors work because they contain americium-241 (the number refers to the radioisotope's mass). Radiation from the radioisotope creates an electric current that weakens when smoke is present, thereby triggering an alarm. Security personnel use the neutrons emitted from californium-252 to inspect airline luggage for hidden explosives, while technicians use the gamma rays from iridium-192 to test the integrity of pipelines. Even polonium-210, the radioisotope that killed former KGB agent Alexander Litvinenko, is used as an anti-static brush to, say, neutralize static electricity on photographic films.

Even more important are the dozens of life-saving radioisotopes used for medical diagnostics and treatments. An estimated 16 million nuclear medicine procedures are performed annually in the United States, primarily to identify cardiovascular disorders, but also to diagnose and treat cancer.

These commercial applications merely hint at the business of radioisotopes, which is also useful for research, the military, and space exploration. Although the private sector conducts most of the commerce, four national laboratories, and in particular Los Alamos, are also players, providing critical radioisotopes that neither industry nor the universities can manufacture.

Guaranteed on Time

Radioactive nuclei first need to be created, but then the atoms that contain the unstable nuclei must be chemically extracted from the target material, purified, packaged safely, and distributed in compliance with Department of Transportation regulations. This production requires a specialized infrastructure: an accelerator or nuclear reactor, where the radioisotopes are made; hot cells, where the radioactive goods are remotely processed and the isotope product purified; and facilities where the radioactive and chemical waste streams are handled.

Los Alamos has been producing radioisotopes since the early 1970s, and its biggest success story has been developing a steady supply of strontium-82 for medical purposes. (See the timeline.) The radioisotope decays to radioactive rubidium-82, a short-lived radioisotope that is used in positron emission tomography (PET) scans to diagnose the condition of a patient's heart.

The Laboratory also produces germanium-68, which is used to calibrate the PET scanners and without which the sophisticated scanners would quickly become less useful.

Up until 1998, those two radioisotopes and others were made using high-energy protons from the accelerator at what is now the Los Alamos Neutron Science Center (LANSCE). The isotope production station was located at the end of the accelerator beam line, so when the accelerator went down for maintenance, radioisotope production ceased.

The situation changed with the 2004 commissioning of the Isotope Production Facility (IPF).

Wolfgang Runde is the new manager of the National Isotope Program, part of which aims to revitalize research into radioisotope products.

"The LANSCE accelerator is actually two linear accelerators joined together," says Gene Peterson, the Chemistry Division leader and driving force behind the IPF. "Someone had the foresight to put a ‘spigot' where the two join. We can remove protons after the first accelerator stage and send them into the IPF's cave. Our operation is effectively decoupled from the other accelerator and from LANSCE."

The protons taken from the spigot have less energy than those that travel the accelerator's full length. The lower-energy actually allowed for more specific control of the nuclear reactions that create the radioisotopes. The decoupling greatly increased the reliability of Los Alamos products and guaranteed the Lab a stake in the national radioisotope market. The Laboratory's Isotope Production and Distribution Program, under which the radioisotopes are produced, is the first business-like operation at Los Alamos.

A National Production Program

As soon as they are created, radioactive nuclei begin to decay and disappear. Part of staying in business is maintaining production to ensure a steady supply.

At the national level, the isotope program, administered by the U.S. Department of Energy's (DOE) Office of Nuclear Energy, is responsible for radioisotope production at Los Alamos, Brookhaven, Oak Ridge, and Idaho national laboratories and ensures the supply through the coordination of production schedules. For example, Brookhaven and Los Alamos—the sole producers of strontium-82 in the country—stagger their schedules so one is producing while the other is down for maintenance.

The Materials Test Station - The proposed Materials Test Station (MTS) is designed to test the behavior of nuclear fuels and materials being considered for advanced nuclear power reactors. It will use high-energy protons from the LANSCE accelerator to create high-energy neutrons, and thereby mimic conditions found inside the reactors. The neutrons and protons would also be available to irradiate radioisotope targets, making MTS the only dual-source radioisotope facility in the world.

The national program has been remarkably successful, in recent years serving about 170 hospitals and companies worldwide and making about 450 isotope shipments annually.

However, the demand for radioisotopes is steadily increasing, with medical isotopes being one of the fastest growing markets. The increased demand has been a significant strain on the enterprise, especially with respect to the supply of radioisotopes used in research.

In response, DOE recently shifted to a contractor-based system, managed out of the newly created National Isotope Program Office. In addition to contracting with the national laboratories, the national program will be keeping the supplies coming through contracts with reactor facilities at the University of California, Davis, and the University of Missouri, as well as with facilities in Russia and South Africa.

"We're trying to establish an integrated production schedule with all the contracted facilities, even those located halfway around the world," says Wolfgang Runde, a Los Alamos chemist and the national program manager. "Plus, we plan to re-invigorate research and development for new radioisotopes, as well as educate the next generation of nuclear physicists, engineers, and chemists. We're investing in the future."

New Life Savers

Los Alamos is already working with several partners to make other life-saving radioisotopes, for example, copper-67, widely available to the medical community. A brief human trial during the 1990s showed that copper-67 was effective for treating non-Hodgkin's lymphoma.

At the time of the trial, it was difficult to consistently produce the radioisotope. Laboratory scientists are investigating using a target enriched in zinc-68 to produce the copper isotope. The reaction is ideally suited for the proton energy range available at the IPF.

Cleo Naranjo with a CardioGen-82 generator containing strontium-82.

The zinc target would also produce copper-64, a gamma-ray emitter that can be used for medical imaging applications. Used together, the two copper radioisotopes offer the possibility of simultaneously diagnosing and treating cancer cells.

Los Alamos is also partnering with the New Mexico Center for Isotopes in Medicine, part of the University of New Mexico, to develop a new and improved gallium-68 generator. The positron-emitting gallium-68 is a short-lived radioisotope that can be used for PET imaging of cancerous tissue. The manufactured generator would contain the long-lived radioisotope germanium-68, which decays to the short-lived gallium-68. A hospital or research institution would use the generator as an on-site source of gallium-68.

The gallium radioisotope can be quickly linked to different cancer-targeting agents. Together with its New Mexico partners, Los Alamos will develop commercial kits that researchers can use to evaluate the gallium-labeled agents in animal studies and experimental models of cancer.

In Runde's opinion, Los Alamos, with its Isotope Production Facility, hot cell facilities, the proposed Materials Test Station, and expertise in nuclear chemistry, radiochemistry, and physics, can be at the forefront of radioisotope research.

"New nuclei will be needed to tackle tomorrow's problems," he says. "We need to start discovering and producing those nuclei today."

• http://isotopes.lanl.gov/
• http://www.ne.doe.gov/isotopes/neIsotopes2a.html"
• “Accelerator Radioisotopes Save Lives – the Isotope Production Facility at Los Alamos”