Effect of photodynamic therapy with verteporfin on tumor blood flow

摘要

The success of photodynamic therapy with verteporfin is partially determined by the pharmacokinetic distribution of the sensitizer at the sensitizer at the time of treatment. In this study tumor blood flow changes in the RIF-1 murine tumor model and tumor response using the regrowth assay were measured, comparing two different intervals (15 min versus 3 h) between drug and light administration. Blood flow measurements were taken with a laser Doppler system monitoring continuously over 1 hour and periodically up to 6 hours after PDT treatment. In the case of the 15-min drug-light interval PDT induced a complete arrest of blood flow by 6 h after treatment. Treatment after the longer interval (3 h) caused significantly less flow decrease, to only 50% of the initial flow in 6 h. Hoechst staining of functional tumor vasculature confirmed the primary vascular damage and the decrease in tumor perfusion. The regrowth rate of tumors treated with 15-min interval was 64% of the regrowth rate of the control group. However, when tumors were treated after the 15-min interval group caused serious damage to the vascular bed of the tumor. These studies support the hypothesis that temporal pharmacokinetic changes in the photosensitizer distribution between the tumor parenchyma and blood vessels can significantly alter the mechanism of tumor targeting during therapy.