Tumor blood-flow changes following protoporphyrin IX-based photodynamic therapy in mice and humans

Abstract

The effects of aminolevulinic acid (ALA)-based photodynamic therapy (PDT) on tumor blood flow are controversial. This study examines the effects of ALA and Photofrin-based PDT on blood flow of Colon-26 tumors implanted in mice as well as the effects of ALA-based PDT on blood flow of human colorectal carcinomas and a carcinoid tumor in situ. Tumors are implanted in both flanks of mice. One tumor of each animal serves as a control. Blood flow is measured using a laser Doppler method. Tumor blood flow in mice not receiving a photosensitizer but treated with three different light fluences (50, 100 and 150 J/cm 2) does not differ significantly from blood flow in the untreated tumor in the opposite flank. PDT after ALA administration using the three different light fluences does not significantly affect blood flow. In contrast, PDT after Photofrin administration causes a significant decrease in tumor blood flow with each light fluence, but this change is not as dramatic as reported in other studies. In contrast to mice, six patients who receive ALA prior to surgery all show a decrease in blood flow (mean=51.8%, p<0.001) after PDT using 100 J/cm 2. Comparison with other published results suggests that it is likely that flow measurement by the laser Doppler method underestimates the effects of PDT on tumor blood flow due to the depth of laser penetration. Nevertheless, the present observations on blood flow suggest that the effects of ALA-based PDT on adenocarcinomas of the colon and rectum as well as an intra-abdominal carcinoid tumor in humans are more pronounced than would be predicated by some animal studies.