A 'Smart Bomb' That Cures

A microscopic cancer "smart bomb" powered by a single radioactive atom is able to find and kill tumor cells in laboratory experiments. Researchers hope to test the technique on human patients next year.

Dr. David A. Scheinberg of Memorial Sloan-Kettering Cancer Center in New York said tests of the technique in mice show that it selectively kills cancer cells and substantially prolongs the life of lab animals with tumors.

"You could inject several million of these molecules and they would circulate around, find their targets cells, be taken inside and then kill the cells," said Scheinberg. "These are extraordinarily potent drugs."

Scheinberg said he hopes to start human clinical trials with the technique next year. He said before the technique could become a routine therapy for cancer patients, researchers need to find out if the low-level radiation will cause unacceptable levels of damage to normal, noncancerous cells.

"We simply can't predict all of that," he said.

A report on the research appears Friday in the journal Science.

Dr. Michael G. Rosenblum, a researcher at M.D. Anderson Cancer Center in Houston, said the Scheinberg study "represents an important advance" in treating cancer using antibodies to target specific cancer cells.

"This doesn't guarantee that it would work in (humans), but it should be taken to the clinic (tested in humans)," said Rosenblum, who is conducting similar studies.

In their study, Scheinberg and his associates created a cancer smart bomb by putting a single atom of actinium-225, a radioactive isotope, inside a microscopic cage made by Dow Chemical Co. in Freeport, Texas.

The isotope is a byproduct of nuclear power plants and nuclear weapons manufacturing. It radiates a low level dose of alpha particles. As it decays, actinium-225 produces three daughter atoms, each of which also gives out alpha particles.

Scheinberg said the cage, made of carbon and nitrogen, is shaped like a ring with the actinium-225 atom inside. They are held together in the same way that magnets can stick together — the isotope has a positive charge and the molecular cage has a negative charge.

"The ring holds the atom in the center like a hula hoop containing a basketball," said Scheinberg.

Attached to the cage and atom is an antibody, a protein that will lock onto a corresponding protein on the surface of a cell. Scheinberg calls the complex a "nanogenerator" because it is small, but still gives off atomic radiation.

When the nanogenerator is injected into the body, it travels through the blood stream until the antibody locks onto a cell and the entire complex moves inside the cell.

Once inside, the alpha particles radiated from the actinium-225 will kill the cell. The additional alpha particles from the daughter atoms can be deadly to nearby cells.

"Each of the daughters can release an alpha particle that can kill a cell," said Scheinberg. "So you get four punches for the same delivery."
Tests exposing the caged atom to laboratory cultures showed that it could kill a variety of cancers, including cells of leukemia, lymphoma, breast, ovarian and prostate cancer.

The researchers also tested the technique in mice that had been injected with human cancer cells. They compared the lifetime of mice treated with the caged atom with that of a control group that was not treated with nanogenerator injections.

Mice that did not receive the nanogenerator therapy lived an average of 43 days before dying of cancer. The mice treated with the nanogenerator lived up to 300 days, with those receiving the highest radiation dose living the longest.

The researchers killed the surviving mice after 300 days and looked for evidence of tumors in their bodies, but found none.

Of particular concern, Scheinberg said, is the effect the nanogenerator might have on normal tissue.

"We depend on the antibody to get it to the tumor, but that process is not 100 percent efficient so there is likely to be some bystander damage (killing of normal cells)," said Scheinberg. "We don't know what that level will be until we test it in patients."

The actinium-225 eventually becomes harmless and remains in the body, he said.

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