Accelerating Isotope Production

If you ran a business that depended on a critical component, how would you feel if the supplier were an aging factory-and no other producer existed? Not good probably. But you might feel better if some enterprising engineers invented a way around the bottleneck. And if the new method generated less waste than the old one, so much the better.

That’s just what’s happened in the case of technetium-99 (Tc-99), a radioactive isotope that is the workhorse of such medical-imaging techniques as single-photon-emission computed tomography. The sole North American source for the isotope is a 40-year-old nuclear reactor in Canada. Temporary shutdowns in 1991 and again last year threatened the supply, sending shock waves through the medical community, says S. James Adelstein, a Harvard University professor of medicine who chaired a 1995 Institute of Medicine report on medical isotopes.

“I think it is intolerable that we are basically being held hostage by one nuclear reactor,” adds MIT’s Lawrence Lidsky, professor of nuclear engineering. So he and his colleagues have developed a way to make Tc-99 and other isotopes that bypasses nuclear reactors. This new method would allow the United States and other countries to develop domestic supplies while minimizing the amount of radioactive waste generated by isotope production.

Technetium was the first artificial element. One of its 17 isotopes, Tc-99 is used in more than 10 million medical procedures a year in the United States alone, according to the Institute of Medicine. With a sixhour half life it doesn’t linger in the body. It can be attached to a medley of carrier molecules and delivered to the bones, heart, kidney, gastrointestinal tract, thyroid gland, central nervous system, and virtually any other body part. Once inside its target, Tc-99 radiates just enough energy to scintillate a scanner, but not enough to damage tissue.

The traditional technique for making Tc-99 begins with a small rolled sheet of so-called weapons-grade uranium. The sheet bakes in a special nuclear reactor where, under intense neutron bombardment, the uranium atoms split into tens of fission products. Technicians then chemically separate any molybdenum-99 that has formed. They dispose of everything else-a grab bag of nasties that includes plutonium, cesium, and strontium-90-as high-level radioactive waste. Finally they pack the purified molybdenum-99 into containers officially called generators but informally dubbed “cows,” that are shipped to radiopharmaceutical companies and hospitals and “milked” every few hours for the Tc-99 that accumulates when the unstable molybdenum-99 nucleus ejects a electron.

This process, now the industry standard, has several drawbacks. “It starts with weapons-grade uranium, requires a nuclear reactor, and finishes with radioactive waste,” says Lidsky. Therefore he and his colleagues in the nuclear engineering department tried approaching molybdenum-99 from a different direction, relying on a well-established principle of theoretical physics called giant dipole resonance.

The MIT process starts with readily available, stable molybdenum-100 and a linear accelerator. Focusing an accelerator’s beam of high-energy electrons onto a small bar of tungsten generates xrays, which consist of photons. A photon with the right energy can then slip inside the nucleus of a molybdenum100 atom and shake up the neutrons and protons, Lidsky explains. The nucleus begins to resonate, or vibrate, and eventually ejects a neutron, becoming molybdenum-99 in the process.

In tests at MIT, the National Institute for Standards and Technology, and the Idaho National Engineering Laboratory, this approach produced enough molybdenum-99 to make commercial generation physically possible. “What really surprised us was that the cost was competitive with the highly subsidized price of molybdenum99 from Canada,” says Lidsky, who had not focused on competitive pricing as a goal.

Lidsky’s alternative may not immediately replace the Canadian supply. To do so, it would have to cost less than current supplies, a difficult task given a heavily subsidized and well-established competitor that needn’t pay the full cost of disposing of radioactive waste. An accelerator-based method, however, could offer a reliable backup in case the flow of molybdenum-99 from Canada dries up, according to Lidsky. And this process “contains all the ingredients for a developing country looking to manufacture its own supply of isotopes without having to build a nuclear reactor or accept shipments of weapons-grade uranium,” says Armando Travelli, who manages the reduced-enrichment reactor program at Argonne National Laboratory.

Now that Lidsky’s team has proved the neutron removal concept, it is turning to other medical isotopes. The linear accelerator method can, for example, generate isotopes that can be made into tiny seeds implanted into prostate, ovarian, and other cancers. The seeds irradiate and kill tumors from the inside out. This method can make isotopes used to ease the racking pain caused by bone cancer. It may also be able to generate isotopes that emit alpha particles (those capable of giving off a helium nucleus) that monoclonal antibodies can deliver directly into cancer cells. This requires a particle with short penetrating ability; alpha particles travel shorter distances than other particles. And, at least in theory, it can make new medical isotopes which can’t be made by any other method and that have yet-unidentified uses.

“Now that we’ve developed the hammer,” says Lidsky, “we are looking for and finding new nails.”