OAK RIDGE, Tenn., Dec. 3, 1996 -- A new method capable of destroying breast tumors without surgery and side effects has been developed at the Department of Energy's (DOE) Oak Ridge National Laboratory (ORNL).
Three ORNL scientists have applied for a patent on this minimally invasive therapy for breast cancer that combines laser light and presently available drugs. When fully developed, the technique will use a focused laser light beam that passes harmlessly through skin and delivers photons in a one-two punch to the target.
The beam of light, two photons at a time, is absorbed by the targeted tumor tissue, activating an ingested pharmaceutical agent that is taken up by rapidly proliferating cells like those found in tumors. The activated agent disables the DNA of the cancer cells, halting their reproduction. Activation of the pharmaceutical agent is limited to the focus of the beam as a result of the unique physics of the photoactivation process called simultaneous two-photon excitation.
The laser light can be focused deep within the tumor tissue, and the drug is activated only in the focus of the beam. Therefore, unlike the case with conventional radiation or chemotherapy, only tumor tissue is affected. Normal tissue is not damaged outside the focus of the beam even on its line of flight entering and exiting the body.
The ORNL scientists have already demonstrated that the technique can selectively kill Salmonella bacteria and human breast cancer cells. The scientists believe the technique could be used to treat skin, liver and breast cancers as well as a variety of other cancers.
By adding specialized molecular biology reagents, the researchers believe that the laser-drug combination can function like a scalpel on genetic material without damaging the cells. Theoretically, the technique could be used to damage the AIDS virus incorporated into human genetic material without damaging the cells of the immune system where it has inserted itself. A variation of this technique can also be used to image breast tumors, thus eliminating the risks of using radiation for mammography.
The ORNL developers of this new approach for "photodynamic therapy" are Craig Dees, molecular biologist; Eric Wachter, physical chemist; Walt Fisher, physical chemist; and Bill Partridge, mechanical engineer and postdoctoral researcher, all in the Health Sciences Research Division and Gil Brown, inorganic chemist, in the Chemical and Analytical Sciences Division.
The idea for the technique emerged one day when Fisher and Wachter saw Dees in the hall and asked him if a special laser technique could have therapeutic applications. Dees thought of the breast cancer application and went to Brown in a room nearby because of his capability of synthesizing drugs that could be activated by laser light.
"The beauty of a national laboratory," says Dees, "is that it gives you the opportunity to bring together the right combination of specialists needed to solve complex problems. Our interdisciplinary team effort has proved to be very productive."
Dees says that many drug companies are trying to alter drugs in their search for a minimally invasive therapy for breast cancer that has no side effects. "What we have done," he adds, "is to change the fundamental activation method so that it more precisely stimulates a drug to destroy a tumor without affecting surrounding, healthy tissue."
A drug that could be used safely with this laser method is 8-MOP, a derivative of psoralen, which is approved by the Food and Drug Administration. Psoralen, a photoactive agent, is normally used with ultraviolet light to treat a variety of skin diseases and near-surface lesions, such as psoriasis and skin cancer. The Oak Ridge scientists believe that many other photoactive agents will work equally well with the new method, opening avenues to the treatment of many other diseases.
"The key to the success of our technique is effecting simultaneous absorption of two photons of low-energy, long-wavelength light within a small volume of tissue," Wachter says. "We can focus the light beam on the targeted area using a lens or mirror that can be adjusted under computer control. The laser light can penetrate the skin with the potential of striking a target at any depth."
In their experiments, the scientists use two lasers. The first is an argon-ion laser that produces visible light in the blue-green range. This light "pumps" the second laser, a mode-locked titanium: sapphire laser, so that it delivers a high frequency pulsed beam of near-infrared light. This red beam is safe--it will illuminate but not harm the skin of your hand. But when focused at a targeted area under the skin, the light pulses have a peak power that can devastate cancerous cells.
"The mode-locked laser produces a beam that has a low average power, but with an exceedingly high peak power that is easily focused into a narrow zone," Wachter says. "As a result, we can target and destroy a cluster of cancer cells and leave normal cells intact. Two-photon laser excitation allows us to achieve pinpoint activation of therapeutic agents in a tightly controlled area. In contrast, commonly used one-photon laser excitation can cause undesirable activation at low intensities and can produce damage over far wider areas than is desired."
In experimental trials, an agarose gel tissue model has been used. A dye was dispersed throughout this thick gelatin material to simulate imaging agent in tissue. When the red beam from the mode-locked laser is focused in the center of the gel, an isolated point of blue light is visible at the focus. The blue dot marks the spot where the dye is fluorescing. It also indicates the point where cancer-cell-destroying chemistry would take place if a phototherapeutic agent was present in actual cancerous tissue. The same ability to focus deep in tissue has been demonstrated in a tumor that was removed from a mouse with breast cancer.
This work was funded by ORNL's Laboratory Directed Research and Development Program.
ORNL, one of DOE's multiprogram research facilities, is managed by Lockheed Martin Energy Research Corp.