Wanted: Medical Isotopes

Science News,  Oct 23, 1999  by Janet Raloff

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Overcoming a critical scarcity of radioactive materials for research

Martin Brechbiel had promising results indicating that a radioactive isotope called bismuth-212 could destroy cancers in laboratory animals. Yet his work at the National Cancer Institute in Bethesda, Md., stopped short in April 1998 when his radioisotope supply suddenly dried up.

Alan R. Fritzberg at NeoRx Corp. in Seattle had also been successfully using bismuth-212 to treat cancers in animal experiments. His work, too, was stopped.

The Department of Energy's Argonne (Ill.) National Laboratory had ceased making the generators that hold radium-224, which decays into lead-212. This isotope eventually decays into the therapeutically active bismuth.

After a 17-month hiatus, DOE arranged for the University of Chicago to send a single generator for Brechbiel's experiments. He will need more. Fritzberg received an extension of his research grant but is still waiting to receive a generator.

Each year, U.S. physicians employ radioisotopes in an estimated 13 million nuclear-medicine procedures and another 100 million laboratory tests. Most of these activities rely on only a few nuclides, principally iodine-131 and technetium-99m.

During the past 5 years, the goals of nuclear medicine have been expanding. Instead of just diagnosing diseases, the field has begun to target the treatment of disorders. This shift has spurred exploration of dozens of uncommon isotopes.

Some can be directed--via antibodies or other small proteins--to particular organs or types of cancer cells (SN: 7/19/97, p. 40). Others, like the bismuth-212 used by Brechbiel and Fritzberg, deliver radiation that enables physicians to knock out diseased tissue while avoiding collateral damage either to nearby healthy cells or to the hospital staff.

The majority of these potentially therapeutic isotopes, unfortunately, can't be ordered from a catalog. Some are created in nuclear reactors. Particle accelerators must generate others. A few of the isotopes, including the radium-224 used to produce bismuth-212, decay from wastes created by production of uranium and plutonium for nuclear weapons.

U.S. scientists, mostly in laboratories created by the Atomic Energy Commission (now DOE), pioneered much of the work on extracting these materials, but 90 percent of the medical isotopes used in the United States today come from foreign vendors, primarily in Canada. Indeed, research on therapeutic isotopes has burgeoned at a time when federal labs have been retiring the facilities needed to make them. Demand for these costly materials now greatly surpasses DOE's ability to supply them. For some short-lived isotopes, no source remains.

As chair of a DOE advisory panel exploring the isotope-availability problem, Richard C. Reba of the University of Chicago has just finished a tour of major U.S. radioisotope-production facilities. Though Reba told SCIENCE NEWS that the isotope-availability picture "continues to look grim, at least for the next 2 or 3 years," he sees signs of improvement. Indeed, a host of new programs has been evolving over the past few years--including several outside DOE--to improve research access to unconventional isotopes.

Unreliable supplies of special radioisotopes have undermined a variety of medical research programs. Like Brechbiel and Fritzberg, Gerald and Sally DeNardo at the University of California, Davis School of Medicine were investigating a potential cancer treatment. They attached copper-67 to antibodies to ferry it to malignant cells. Their protocol, which required each patient to receive a copper-67 treatment monthly for 4 months, showed promise against non-Hodgkin's lymphomas resistant to conventional therapies.

The only sources of the isotope in the United States were particle accelerators at DOE labs, where copper-67 was occasionally made by piggybacking its production onto some other activity--typically a physics or nuclear-weapons experiment.

"Because of restricted budgets, [the labs] were unable to operate the accelerators year round, so it became a logistics nightmare to get the patients lined up at the same time the accelerators could make copper-67," says Owen Lowe, associate director of isotope programs at DOE.

DOE's inability to produce the isotope reliably led the Davis scientists to abandon their study, Lowe says.

Researchers using two other radioisotopes, platinum-193 and xenon-127, similarly gave up on their projects when supplies of these became erratic or unavailable, says Reba.

Some potential therapies don't even make it off the drawing board. Time and again, researchers request an isotope for drug-development or -treatment studies only to learn it's not available, says Carol S. Marcus, a consulting scientist and former director of the nuclear-medicine outpatient clinic at Harbor-UCLA Medical Center in Torrance, Calif.

Last year, DOE convened an expert panel to forecast what future U.S. demand for unconventional medical isotopes might be if research were to proceed unimpeded. It found that use of these, including unconventional therapeutic isotopes, could grow 7 to 14 percent per year. In 20 years, the fledgling therapeutic nuclear-medicine industry could be valued at as much as $1.1 billion annually, it found.