19 November 2003This fall, Siemens AG (Munich, Germany) announced that it had licensed technology to produce devices that fire carbon-12 (12C) ions at cancerous tumors in an attempt to kill them in one shot rather than in weeks of treatment with conventional radiation devices. Siemens says its aim is to bring the technique, whose first applications will likely be the treatment of hard-to-reach cancers near vital organs such as the brain or spinal cord, to hospitals within three years.
Researchers and clinicians have long known that high-energy particles are an ideal weapon for attacking cancerous cells because, when delivered in concentrated bursts, they overwhelm the built-in repair mechanisms of cells. Despite this knowledge, the effectiveness of such therapy was limited by the high cost, large size, and relative clumsiness of the tools at hand. But recent advances have now made it possible to pinpoint the placement of protons and ions of various elements, while strides are being made in the development of lasers that may turn these bank-busting behemoths into compact, inexpensive devices.
Hitting the bulls-eye
Siemens technique uses a particle accelerator to bring the 12C ions to energies as high as 300 MeV before magnets precisely beam them at the target. This is an improvement over traditional radiation therapy, in which photons or electrons are fired at a tumor, because the amount of energy with which the ions are fired can be fine-tuned, allowing clinicians to pinpoint the placement of a dose of radiation to within a millimeter. With this level of precision, a high-intensity dose can be trained on the malignant cells while sparing the surrounding healthy tissue.
Precision relates to particle energy in a fairly simple way. Because of their tremendous starting energy, the carbon ions are moving so rapidly when they first enter the body that there is very little interaction with the cells they pass on the way to the site of the tumor. Since most of the volume of a cell is empty space with subatomic particles such as electrons moving around rapidly, chances are good that a fast-moving ion can move through a cell without getting near enough to the its constituent parts to strip away some of its electrons. But as the ions lose energy, they slow down, extending the interaction time with nearby cells.
The ions effect on these cells increases steadily until, in the instant before they come to a complete stop, the energy transfer between the accelerated particles and the surrounding cells is greatest. Giving the ions a relatively low starting energy, say 70 MeV, would target a tumor near the surface, such as in the eye. But a 200 MeV shot would hit deep-seated malignancies.
In traditional radiation therapy using X-rays or gamma rays, the opposite is true. The energy level of the photons (about 250 keV) or electrons (around 20 MeV) is so low that they immediately react with cells of the skin, fat, and any organs in the beams path. This dose distribution creates several disadvantages. By the time the beam reaches the tumor, most of the energy in the photons has been exhausted in damaging healthy tissue, leaving precious little for destroying the rapidly dividing cancer cells.
Also, some of the particles overshoot the tumor, irradiating healthy tissue behind it. To limit the damage inflicted on normal cells, the number of particles fired at the tumor has to be limited, increasing the odds that the cancerous cells will survive the series of barrages during the two or three dozen sessions in a round of radiation therapy.
Heavy ions beat standard radiation therapy for another reason. Because of their mass, they inflict far more damage on the cells with which they interact than, say, photons, which carry energy but have no mass. The difference in destructive power, known as radiobiological effectiveness, or RBE, is important. Although the self-repair mechanisms in cancerous cells are frequently not as efficient as a healthy cells, there is a period during a malignant cells life cycle when its resistance to traditional radiation therapy is far greater than normal.
Carbon ions, which create clusters of damage, especially to a cells DNA strands, eliminate this variability in effectiveness. According to Eros Pedroni, a physicist in the department of radiation medicine at the Paul Scherrer Institute of Physics (Villigen, Switzerland), the RBE of carbon ions is high enough so that, under the right circumstances, it will be a "one-hit, one-kill" treatment. Patients would need to go to the hospital only once or twice before the cancer is eliminated instead of 20 or 30 times.
But Pedroni cautions that heavy-ion therapy has not yet reached the point where there is enough clinical experience to say which cancers it should be used to attack or at what doses. Siemens and the research institutes with heavy-ion accelerators are working to identify the cases where patients can benefit from 12C therapy and to chart the effects of various dosages and energy levels.