- The Washington Times - Friday, November 16, 2001

Researchers in New York have developed a radiation cancer treatment that works like one of the Pentagon's "smart bombs" by locating, invading and selectively killing cancer cells.
The experimental therapy, devised by scientists at the Memorial Sloan-Kettering Cancer Center (MSKCC), and so far tested only in cell cultures and mice, consists of a single radioactive atom contained inside a microscopic cage.
Unlike conventional radiation therapy, which attacks tumors from the outside, this new system releases a cascade of atomic fragments known as alpha particles inside cancer cells.
In a report published in this week's issue of the journal Science, Dr. David A. Scheinberg, the study's senior author, and his MSKCC research colleagues disclosed that the experimental group of mice injected with human cancer cells and treated with the smart-bomb therapy lived up to 300 days. That compared with an average life span of 43 days for the control group of mice with cancer that was not given the low-level radiation treatment.
Also, the researchers killed the surviving mice after 300 days and found no evidence of tumors in their bodies, said Dr. Scheinberg, chief of MSKCC's Leukemia Service and head of the Sloan-Kettering Institute's Laboratory of Hematopoietic Cancer Immunochemistry.
"We have found an effective way of containing and then delivering this highly potent [radioactive] element directly into cancer cells," said Dr. Scheinberg.
He added that he and his team intended to file an application with the U.S. Food and Drug Administration to begin human safety trials of their system, which they called a nanogenerator, sometime next year.
The new therapy, administered by injection, gets its name from the fact that it is small and gives off atomic radiation, Dr. Scheinberg said.
The nanogenerator consists of a single atom of actinium-225, a radioactive isotope that is a byproduct of nuclear power plants and nuclear weapons manufacturing.
The isotope is inside a molecular cage made of carbon and nitrogen, fabricated by Dow Chemical Co. in Freeport, Texas.
The cage is attached to antibodies, which are proteins that target specific cancer cells and which lock onto corresponding proteins in those cells.
When the antibody locks onto a cancer cell, the entire nanogenerator moves inside the cell.
As the actinium-225 decays, it gives off short-lived, highly energized alpha particles that stream through cancer cells and kill them by destroying their genetic material, or DNA, and proteins.
While the actinium-225 decays, it produces three "daughter" atoms as well, which also emit alpha particles that can be lethal to nearby cells.
Each daughter cell can release an alpha particle that can kill a cell, so "you get four times the punch from one atom," said Dr. Scheinberg.
The investigators tested the nanogenerator in cell cultures in a variety of human cancer types: leukemia, lymphoma, breast, ovarian, neuroblastoma and prostate. They found that the device could kill all these forms of cancer even at "extremely low concentrations."
In the mice studies, the nanogenerator was effective against both prostate cancer and disseminated, or widespread, lymphoma. "All of the animals had their lives extended after a single treatment at a low dose," said Dr. Scheinberg.
"Nanogenerators targeting a wide variety of cancers may be possible," the researchers wrote in an introduction to their report in Science.
Leukemia most likely will be the first cancer tested for the new technology in human trials, Dr. Scheinberg said, because his team has the most experience targeting those cancers.
While mice treated via the nanogenerator seemed to experience no side effects, Dr. Scheinberg cautioned that the true test of its effectiveness would not be known until the human trials began. Of particular concern, he said, is whether it causes harm to normal tissue, and if so, to what extent.
Joanne Schellenbach, spokeswoman for the American Cancer Society, said of the study's findings: "You have to be encouraged, but also cautious."
She noted that "results of animal studies cannot always be easily replicated in humans."
In fact, she said, "not a large percentage" of promising results in animal studies "pan out" for use in humans.


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