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 Huntsville, Alabama.
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.