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 proces 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; Gil Brown, organic chemist; and Bill Partridge,
mechanical engineer and postdoctoral researcher, all in the Health Sciences
Interdisciplinary Collaboration Led to New Method
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 discuss it with 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 FDA. 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
Key to Treatment's Success
"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 illuminates but does not harm the skin.
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," says Wachter. "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 the
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 were 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