The idea is to take a radioactive atom, put it in a molecular cage and attach it to an antibody molecule that carries it inside specific cancer calls. Radiation then can destroy the cancer cell with maximum effect.
The "atomic nanogenerator," as it is called, has worked well in animal models, and an application for use against human cancers will be filed soon with the Food and Drug Administration, says the leader of the research group, Dr. David A. Scheinberg, head of the Memorial Sloan-Kettering Cancer Center laboratory of hematopoietic cancer immunochemistry."Targeting isotopes to tumors is an old idea, two or three decades old," says Scheinberg. "Making this generator was an idea dating to the mid-90s, among a number of investigators."
To make the idea a reality, "we needed a source of isotope for the generator, a stable molecular cage to hold it, an antibody to deliver it, and a biological and biochemical understanding of how it would work," Scheinberg says.
The nanogenerator, as described in a report in the Nov. 16 issue of Science, uses radioactive atoms of the element actinium, which give off alpha radiation, very small, high-energy particles that decay to produce "daughter" atoms that emit their own alpha particles. The molecular cage for the actinium atom was developed with help by chemists at the Dow Chemical Company.
A key to success was development of the antibody molecules that carry the nanogenerator to the target cancer cells, and a way of attaching the radioactive atoms to the antibodies. That work took eight years, Scheinberg says.
Using a variety of antibodies, the researchers were able to kill human leukemia, lymphoma, breast, prostate and ovarian cancer cells in laboratory dishes. They then successfully tested the treatment in two mouse models, involving prostate cancer and lymphoma.
The first human trials probably will be against leukemia; Scheinberg is chief of the Memorial Sloan-Kettering leukemia service. "Prostate cancer and lymphoma will be next," he says.
One major advantage of using actinium is that it has a relatively long half-life, meaning that the nanogenerators could be manufactured at a central pharmacy for distribution to physicians. Another advantage is that it is a by-product of waste from nuclear power plants, so that it is readily available.
The doses necessary for human treatment are likely to be small, Scheinberg says -- "probably so small that the injections could be done in a doctor's office or outpatient hospital clinic."
The theory behind the practice of radioimmunotherapy, as the field is often called, is simple, says George Chen, director of radiation physics at Massachusetts General Hospital in Boston: "Alpha particles have high energy transfer, so they do a considerable amount of DNA damage. By incorporating a radioactive particle in a biological molecule that specifically attaches itself to a cancer cell, you can deliver radiation to the cells where you need the radiation."
Other efforts in the field are underway, Chen says. For example, University of Chicago researchers have looked into the use of alpha particle radiation for the treatment of ovarian cancer.
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The exact dosages and the effectiveness of the technology in treating patients still must be determined, Scheinberg cautions. "It is still early in its development, so predictions on its ultimate use or effectiveness are still premature," he says.
For information about current methodsof radiation therapy for cancer, consult the American Society for Therapeutic Radiology and Oncology or the National Cancer Institute.