Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy

During the process of photodynamic therapy (PDT), problems arise such as stasis or occlusion of microvasculature, tumor oxygen depletion, and photosensitizer bleaching. This study shows that the first problem could be reduced by using a lower fluence rate light source in PDT. Microvasculature damage was studied experimentally in hematoporphyrin derivative–mediated PDT against light fluence rate, and, to some extent, less microvasculature damage was induced under 75 mW/cm² illumination than under 150 mW/cm². Histology of vessels at the end of PDT showed that vessel damage could be observed in both groups, indicating that the microvasculature would eventually be damaged as long as the administration of light fluence was sufficient and regardless of the illuminating fluence rates. Thus microvasculature damage induced by low fluence rate illumination could also be effective in tumor control after PDT. The cell-killing experiment was performed in vitro and designed so that cell-killing rate was influenced only by light characteristics. The higher cell-killing rate caused by 75 mW/cm² illumination indicated that lower fluence rate light could enhance the light absorbency or decrease the bleaching of photosensitizer.