Laser-Drug Combination May Treat Breast Cancer Without Surgery

A new method capable of destroying breast tumors without surgery andside effects has been developed at the Department of Energy's (DOE) OakRidge National Laboratory (ORNL).

Three ORNL scientists have applied for a patent on this minimally invasivetherapy for breast cancer that combines laser light and presently availabledrugs. When fully developed, the technique will use a focused laser lightbeam that passes harmlessly through skin and delivers photons in a one-twopunch to the target.

The beam of light, two photons at a time, is absorbed by the targetedtumor tissue, activating an ingested pharmaceutical agent that is takenup by rapidly proliferating cells like those found in tumors. The activatedagent disables the DNA of the cancer cells, halting their reproduction.Activation of the pharmaceutical agent is limited to the focus of the beamas a result of the unique physics of the photoactivation proces and breastcancers, as well as a variety of other cancers.

By adding specialized molecular biology reagents, the researchers believethat the laser-drug combination can function like a scalpel on geneticmaterial without damaging the cells. Theoretically, the technique couldbe used to damage the AIDS virus incorporated into human genetic materialwithout 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; WaltFisher, physical chemist; Gil Brown, organic chemist; and Bill Partridge,mechanical engineer and postdoctoral researcher, all in the Health SciencesResearch Division.

Interdisciplinary Collaboration Led to New Method

The idea for the technique emerged one day when Fisher and Wachter sawDees in the hall and asked him if a special laser technique could havetherapeutic applications. Dees thought of the breast cancer applicationand went to discuss it with Brown in a room nearby because of his capabilityof synthesizing drugs that could be activated by laser light.

"The beauty of a national laboratory," says Dees, "isthat it gives you the opportunity to bring together the right combinationof specialists needed to solve complex problems. Our interdisciplinaryteam effort has proved to be very productive."

Dees says that many drug companies are trying to alter drugs in theirsearch for a minimally invasive therapy for breast cancer that has no sideeffects. "What we have done," he adds, "is to change thefundamental activation method so that it more precisely stimulates a drugto destroy a tumor without affecting surrounding, healthy tissue."

A drug that could be used safely with this laser method is 8-MOP, aderivative of psoralen, which is approved by the FDA. Psoralen, a photoactiveagent, is normally used with ultraviolet light to treat a variety of skindiseases and near-surface lesions, such as psoriasis and skin cancer. TheOak Ridge scientists believe that many other photoactive agents will workequally well with the new method, opening avenues to the treatment of manyother diseases.

Key to Treatment's Success

"The key to the success of our technique is effecting simultaneousabsorption of two photons of low-energy, long-wavelength light within asmall volume of tissue," Wachter says. "We can focus the lightbeam on the targeted area using a lens or mirror that can be adjusted undercomputer control. The laser light can penetrate the skin with the potentialof striking a target at any depth."

In their experiments, the scientists use two lasers. The first is anargon-ion laser that produces visible light in the blue-green range. Thislight "pumps" the second laser, a mode-locked titanium:sapphirelaser, so that it delivers a high-frequency pulsed beam of near-infraredlight. This red beam is safe--it illuminates but does not harm the skin.But when focused at a targeted area under the skin, the light pulses havea 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 narrowzone," says Wachter. "As a result, we can target and destroya cluster of cancer cells and leave normal cells intact. Two-photon laserexcitation allows us to achieve pinpoint activation of therapeutic agentsin a tightly controlled area. In contrast, commonly used one-photon laserexcitation can cause undesirable activation at low intensities and canproduce damage over far wider areas than is desired."

In experimental trials, an agarose gel tissue model has been used. Adye was dispersed throughout this thick gelatin material to simulate theimaging agent in tissue. When the red beam from the mode-locked laser isfocused in the center of the gel, an isolated point of blue light is visibleat the focus. The blue dot marks the spot where the dye is fluorescing.It also indicates the point where cancer cell-destroying chemistry wouldtake place if a phototherapeutic agent were present in actual canceroustissue. The same ability to focus deep in tissue has been demonstratedin a tumor that was removed from a mouse with breast cancer.

This work was funded by ORNL's Laboratory Directed, Research and DevelopmentProgram.