One obstacle encountered in the laser activation of photodynamic therapy is due to the limited penetration into tissue of laser light at the optimum photosensitizer activation wavelength. In the optimum case the tissue surrounding the tumor would be transparent to the wavelength of light employed while the photosensitizer concentrated in the tumor was highly absorptive. Unfortunately this situation is not encountered in practice. For example, the absorption maximum of the photosensitizer HpD occurs at about 400nm. At this wavelength hemoglobin, beta- carotene, and melanin are all also strongly absorbent, leading to rapid attenuation of the photoradiation in tissue. Use of longer wavelengths increases the depth of penetration of the radiation at the expense of photosensitizer activation efficiency. Recent experimental evidence suggests that it may be possible to saturate the hemoglobin chromophore in tissue, thus increasing the effective penetration depth in tissue, by using pulsed laser light. On the other hand, independent research has indicated that reverse saturable absorption occurs in dihematoporphyrin ether at 628nm when irradiated with a pulsed laser. These results, taken as a whole, suggest that it may be possible to use these non-linear effects simultaneously in order to optimize PDT. It is proposed to investigate the optical non-linearity of the photosensitizer DHE and hemoglobin using a frequency doubled, Q-switched Nd:YAG laser (532nm). Standard absorption/transmission measurements will be made over a range of peak powers in order to measure saturable effects. It is expected, if positive results are obtained. that the efficacy of PDT could be significantly improved by making use of these non- linear saturation effects.
