In the present study, the effects of
photodynamic therapy (
PDT) with
verteporfin on
tumor blood flow and
tumor regrowth were compared as
verteporfin distributed in different compartments within the RIF-1
tumor. Tissue distribution of
verteporfin was examined by fluorescence microscopy, and blood flow measurements were taken with a
laser Doppler system. It was found that, at 15 min after
drug administration, when
verteporfin was mainly confined within the vasculature,
PDT induced a complete arrest of blood flow by 6 h
after treatment.
PDT treatment at a longer
drug-light interval (3 h), which allowed the
drug to diffuse to the
tumor interstitium, caused significantly less flow decrease, only to 50% of the initial flow in 6 h. A histological study and
Hoechst 33342 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
PDT was 64% of that of the control group. However, when
tumors were treated with 3-h interval
PDT, the regrowth rate was not significantly different from that of the control, indicating that only the 15-min interval
PDT caused serious damage to the
tumor vascular bed. These results support the hypothesis that temporal pharmacokinetic changes in the distribution of the
photosensitizer between the
tumor parenchyma and blood vessels can significantly alter the
tumor target of
PDT.