New drugs zap cancer cells with radiation.

Radiation and chemotherapy have long been the most potent anticancer weapons. Now, researchers are testing drugs that combine the two techniques and may one day act as smart bullets for treating certain kinds of cancer. At the American Association for the Advancement of Science meeting in Seattle this week, scientists discussed these drugs-radioactive atoms chemically attached to antibodies. The antibodies seek out and bind to specific proteins on the surface of cancer cells.

Unlike total body irradiation, the drugs bring radiation to bear directly on cancerous areas, reducing healthy tissue's exposure. The drugs might effectively treat cancers like leukemia, in which diseased cells are dispersed throughout the bloodstream, with fewer side effects than traditional remedies. Janet F. Eary of the University of Washington Medical Center in Seattle described her team's studies of a treatment for leukemia and lymphoma that uses an antibody carrying iodine-131. These atoms emit highly penetrating gamma rays, which destroy tumor cells but also damage healthy tissue. Taking a newer approach, a team at the Memorial Sloan-Kettering Cancer Center in New York focuses on the isotope bismuth-213, which gives off alpha particles when it decays. The researchers attach single atoms of Bi-213 to antibodies that target CD33, a protein on the surface of myeloid leukemia cells.

Alpha particles are helium nuclei, which are much heavier than other forms of radiation and don't travel very far. "One of the appealing features is that the radiation is confined to one or two cell diameters," says David A. Scheinberg, chief of the leukemia service at Sloan-Kettering. Because many antibodies can attach to a single cancer cell, the new drug delivers an estimated 50,000 times more radiation to the leukemia cells than to noncancerous tissues.

The short range of effectiveness, however, may limit the types of cancer that can be treated with the method. The alpha particles probably won't penetrate large, solid tumors. The technique could work on cancers that have spread throughout the body or those characterized by many small clusters of cells, such as ovarian cancer.

In choosing a particular radioactive atom to use, says Joel M. Tingey, a chemist at the Pacific Northwest National Laboratory in Richland, Wash., "you have to look at several different effects: its half-life, what type of radiation [it emits], how long it stays in the body, and where it goes. You have to look at what it's going to decay into and the effect of those things on the body." Half of the Bi-213 decays in just 47 minutes; most of it is gone in a few hours.

Part of the challenge in developing these drugs is chemically binding the radioactive atoms to the antibodies. Bi-213 is "attached through a [linker molecule] known as DTPA, which is like a little cage that holds it in place," Scheinberg says. The Bi-213 can be linked to the antibody in as little as 6 minutes and can be done where patients are being treated-essential factors when using an isotope with such a short half-life. Waiting too long to inject the drug into a patient would render most of it ineffective.

A clinical trial for the Bi-213 antibody has just begun, so the researchers don't yet know how effective the method is or whether patients will suffer significant side effects. So far, the study has shown that the drug is not acutely toxic and that it reaches the cancer cells in a few minutes.