MILWAUKEELight-emitting diodes (LEDs) developed by NASA
for commercial plant growth research on the space shuttle are being
used to remove brain tumors through photodynamic therapy. Harry
Whelan, MD, and his colleagues have used the new LED red-light probes
and the light-activated drug porfimer sodium (Photofrin) to attack
difficult brain tumors in three patients. So far, all are doing
extremely well, Dr. Whelan said in an interview with ONI.
We are hopeful that the LEDs long, cool wavelengths of
light were able to penetrate wide enough and deep enough to get rid
of the tumor for good, said Dr. Whelan, professor of neurology,
pediatrics, and hyperbaric medicine, Medical College of Wisconsin, Milwaukee.
The first patient Dr. Whelan treated, a 20-year-old woman with
anaplastic ependymoma, had undergone six previous surgeries over 10
years, as well as radiation and chemotherapy. Dr. Whelan treated her
recurrent tumor in May 1999 with the porfimer/LED combination.
She has fully recovered with no complications and no evidence
of the tumor coming back, he said.
The second patient, a 21-year-old man with anaplastic astrocytoma,
was treated in August 1999 and is doing well with no evidence of
tumor recurrence, Dr. Whelan said.
The third patient, a 17-year-old boy with brain stem glioma, was
treated in November 1999. He is already regaining strength
previously lost due to tumor-induced hemiplegia, Dr. Whelan
said. The patients are being followed with regular clinical
examinations and magnetic resonance imaging.
Cooler, Cheaper Than Lasers
Previous photodynamic therapies have used lasers to activate the
photosensitive, tumor-killing drugs, but lasers generate relatively
short wavelengths of light. The new LED probe uses longer wavelengths
that penetrate through nearby tissues, reaching parts of the tumor
that laser light cannot reach. In addition, the longer wavelengths
are cooler than the shorter laser light wavelengths, reducing the
chance of injury to normal brain tissue near the tumor.
The LED Probe
The LED probe consists of a 10-cm hollow steel tube with 144 tiny LED
chips arranged in a cylinder (see Figure
1 and Figure 2 ). The tube
contains three channels: one supplying insulated wire to provide
electricity for the LED tip, one to provide sterile water to cool the
tip, and one to provide intralipid fluid used to inflate a tiny
balloon at the end of the probe that helps scatter the light uniformly.
Dr. Whelan said that this type of LED probe can be purchased
for a fraction of the cost of a laser and can be used for hours
while still remaining cool to the touch. The entire light source and
cooling system is about the size of a briefcase. Furthermore, due to
its relative safety, repeat treatments are possible.
The probe was developed for photodynamic cancer therapy by Quantum
Devices Inc. (Barneveld, Wisconsin) under a NASA Small Business
Innovative Research program grant, part of NASAs Technology
Transfer Department at the Marshall Space Flight Center in
Photodynamic therapy of solid tumors requires a photosensitizer that
selectively localizes in malignant cells vs normal cells and is
activated by a light that can penetrate deeply into solid tissue. The
photosensitizer is injected into the tumor area and, when activated
with a light source, causes the generation of free radicals, which
kill the tumor cells.
In general, light penetration in the brain and other solid
tissues increases for light with longer wavelengths, so effective
treatment requires a photosensitizer that absorbs light
preferentially at long wavelengths, Dr. Whelan said.
He explained that the preferential accumulation of these compounds is
due to the fact that fast-growing tumor cells have a greater
requirement for porphyrins than do normal cells. Verma et al
suggested that this may reflect the fact that cancer cells have
elevated levels of mitochondrial benzodiazepine receptors, which bind
porphyrins with high affinity (Molecular Medicine 4:40-45, 1998).
Dr. Whelans initial studies used Photofrin as the photoactive
drug. This drug is currently approved in the United States for
treatment of certain lung and esophageal cancers. Future studies are
expected to use second-generation photosensitizers such as lutetium
texaphyrin (Lutex) and benzoporphyrin derivative (BPD). These agents
are activated at wavelengths that overlap those achieved with newer
LED chips (630 nm to 940 nm).
Lutex and BPD have major absorption peaks at 730 nm and 680 nm,
respectively, which gives them two distinct advantages, Dr.
Whelan said. First, longer wavelengths of light penetrate brain
tissue more easily so that larger tumors could be treated. Second,
the major absorption peaks mean that more of the drug is activated
upon exposure to light.
Tumoricidal effects of Lutex and BPD have been studied in vitro using
canine glioma and human glioblastoma cell cultures, Dr. Whelan said.
Using LEDs with peak emissions of 728 nm and 680 nm as a light
source, a greater than 50% cell kill was measured in both cell lines
by tumor DNA synthesis reduction. Based on the maximum
tolerated dose of Lutex and BPD in dogs, human trials are now
anticipated, he said.
Another area of interest is in how the photosensitizer is delivered.
Dr. Whelan used an aqueous formulation of Photofrin in the patients
he treated, but other researchers have reported that liposomal
formulations are more effective than aqueous formulations in cell
culture studies. We have successfully tested and published data
on a liposomal BPD formulation, Dr. Whelan said.