Light-emitting Diodes as a Light Source for Intraoperative Photodynamic Therapy

Abstract

The development of more cost-effective light sources for photodynamic therapy of brain tumors would be of benefit for both research and clinical applications. In this study, the use of light-emitting diode arrays for photodynamic therapy of brain tumors with Photofrin porfimer sodium was investigated. An inflatable balloon device with a light-emitting diode (LED) tip was constructed. These LEDs are based on the new semiconductor aluminum gallium arsenide. They can emit broad-spectrum red light at high power levels with a peak wavelength of 677 nm and a bandwidth of 25 nm. The balloon was inflated with 0.1% intralipid, which served as a light-scattering medium. Measurements of light flux at several points showed a high degree of light dispersion. The spectral emission of this probe was then compared with the absorption spectrum of Photofrin. This analysis showed that the light absorbed by Photofrin with the use of the LED source was 27.5% of that absorbed with the use of the monochromatic 630-nm light. Thus, to achieve an energy light dose equivalent to that of a laser light source, the LED light output must be increased by a factor of 3.63. This need for additional energy is the difference between a 630- and 677-nm absorption of Photofrin. Using the LED probe and the laser balloon adapter, a comparison of brain stem toxicity in canines was conducted. LED and laser light showed the same signs of toxicity at equivalent light energy and Photofrin doses. The maximal tolerated dose of Photofrin was 1.6 mg/kg, using 100 J/cm2 of light energy administered by laser or LED. This study concludes that LEDs are a suitable light source for photodynamic therapy of brain tumors with Photofrin. In addition, LEDs have the potential to be highly efficient light sources for second-generation photosensitizers with absorption wavelengths closer to the LED peak emission.

Preclinical Evaluation of Benzoporphyrin Derivative Combined with a Light-Emitting Diode Array for Photodynamic Therapy of Brain Tumors

“…Our laboratory uses a posterior fossa canine model for evaluation of normal brain stem toxicity [8, 16]. Previously, we have shown that Photofrin using laser light or LED light can cause fatal brain stem toxicity [8, 16].…”

“…The MTD was 1.6 mg/kg of Photofrin and 100 J/cm 2 of 630-nm laser light [8]. In the subsequent study, we used a broad-spectrum LED balloon adapter light source and found the same MTD [16]. In both studies, severe brain stem toxicity occurs if the MTD is exceeded.…”

“…LED are based on semiconductor technology that was originally developed to grow plants during space flight [18, 19, 20]. In a previous study, we showed that LED can be used to perform PDT with Photofrin [16]. Because of the longer central wavelength of BPD versus Photofrin (690 vs. 630 nm), dosimetry using the LED probe had to be adjusted.…”

“…For the in vivo PDT experiments, an LED probe with an inflatable balloon tip was utilized [16]. The LED technology used in these experiments was originated by NASA and Quantum Devices Inc. (Barneveld, Wisc., USA) for plant growth experiments in space [18, 19, 20].…”

“…It preferentially accumulates in brain tumors as compared to normal tissue [13, 14]. Upon activation with laser light at 630 nm, Photofrin destroys brain tumors in animal models and humans [5, 6, 7, 8, 15, 16]. Although the initial results were very encouraging, treatment failure did occur.…”