Electroporation "Knife" for Cancer

4 February 2009—Electroporation, a technique that microbiologists have long used experimentally to temporarily punch holes in cell membranes and ferry drugs or genes into them, may yield new benefits for cancer treatment, according to medical-device firm AngioDynamics, in Queensbury, N.Y. Last month, the company showed off an electroporation device that it claims can kill cancerous tumor cells with remarkable specificity while inflicting little or no damage on surrounding structures and causing no pain for the patient.

Such claims, if they hold up, would have a tremendous impact on a cancer surgery technique called tumor ablation, in which doctors rely on either chemical treatments or an array of techniques that heat up or cool down the tumor tissue until it succumbs. Because they kill with temperature, these therapies affect all tissue indiscriminately, wiping out blood vessels along with the cancer cells and potentially causing bleeding. Electroporation, on the other hand, does not produce enough heat to disrupt nearby tissue.

”Most procedures take a soft egg and boil it,” says Stephen Kee, a radiologist at the University of California at Los Angeles Medical Center, who has been testing the device with guidance and funding from AngioDynamics. ”To us, the real Achilles’ heel of ablation techniques is the destruction of blood vessels.”

When tumors abut especially large blood vessels, another problem arises for thermal ablation, says Kee. Radiologists call it the heat sink effect. The flow of blood provides convection to the area, cooling it substantially, and it becomes more difficult to maintain temperatures that thoroughly and consistently ablate the tissue. AngioDynamics’ device, the NanoKnife, might circumvent this problem all together.

The NanoKnife delivers quick bursts of energy through a set of electrodes inserted into and around the tumor. The pulses can last up to 100 microseconds and create an electrical field of up to 3000 volts per centimeter. A cell within range of the electric field will form pores in its fatty membrane, allowing ions to rush through. When electroporation is performed with a lower voltage than the NanoKnife delivers, and with single pulses instead of a train of pulses, the pores will eventually close as the electric potential of the cell stabilizes. Microbiologists have used this kind of reversible electroporation, among many other things, to transport genetic material into stem cells. When exposed to higher voltages and longer pulse duration, however, the pores in the cell membrane remain open and cause the cell to initiate a programmed suicide, known as apoptosis.

The electroporator works with both unipolar and up to six bipolar electrodes. Proper placement largely determines how successful the ablation will be, especially with the bipolar electrodes, which must be spaced correctly in order to produce a spherical electrical field. Complicating things further is the fact that the conductivity of tissue varies from organ to organ.

Mark Ortiz, the vice president of business development for AngioDynamics, says that the company is working on software that would standardize a treatment-planning protocol. He projects that medical imaging will provide information on tissue type and tumor dimension that the software will then use to automatically produce a scheme for placing electrodes and what generator settings to use.

The impact that irreversible electroporation has on blood vessels is still being researched. Studies show that they remain structurally intact, but it’s not yet clear how much damage the blood vessels endure. A study published in 2007 in Technology in Cancer Research and Treatment found that the procedure killed a large proportion of vascular smooth muscle cells—cells that line the walls of blood vessels and cause them to contract—when directly applied to the carotid artery. But the study also found that the structures that connect these cells and form the basic architecture of the vessels remained intact.

To date, the safety of the device has been shown through the experience of only a handful of patients. The NanoKnife has already been approved in the United States for use in the ablation of soft tissue, and AngioDynamics has installed prototypes in 17 medical centers around the world, 5 of which are actively using it. The device has been tested so far on 37 patients.

Ken Thomson, a radiologist at Alfred Hospital, in Melbourne, Australia, has used the NanoKnife to destroy kidney and lung tumors. He says that the patients who will benefit most from this device are those whose tumors have snuggled up next to vital blood vessels or airways. In these cases, the risks of attacking the tissue with heat are high, and electroporation provides a new alternative. Thomson has applied the technique to at least two patients whom he says would never be candidates for thermal ablation, and he has watched their tumors recede with only a Band-Aid to show for it.

”It’s just an amazing concept that you can do this,” he marvels. ”There’s nothing else that will do this.”

Though electroporation provides a new alternative, doctors are having some success with thermal ablation, too. Francesco Garbagnati, the director of radiology at the National Cancer Institute of Milan, specializes in radio-frequency thermal ablation and has been using low-wattage and very thin electrodes to work on blood-vessel-rich parts of the liver. He is skeptical of electroporation. ”We are having very good results around blood vessels,” he says, adding, ”I don’t think [electroporation] could solve this problem.”