Real-Time Visualization and Quantitation of Vascular Permeability In Vivo: Implications for Drug Delivery
A. Representative fluorescence micrographs from two human HEp3 tumors displaying peri-tumoral (i) and tumor core (ii) vascular leak are shown with the 2000 kDa FITC-dextran (green) and 158 kDa TRITC-dextran (red). The normalized images were generated by subtracting the 0 hour image from the 3 hour image, and represent the net vascular leak. Tumor induced vascular leak is localized primarily to the tumor and especially to the central, necrotic core of the tumor. B. Areas utilized for regional vascular leak analyses are delineated. The solid circle represents an area of non-tumor tissue; the dashed circle denotes tumor and the dotted line indicates the avascular necrotic core. C. Quantitation of leak of large (green) and small (red) dextrans is shown for non-tumor tissue, the entire tumor and the core of the tumor. The relative leak of both dextrans was normalized to time zero; n = 6 for each analysis. Two-way ANOVA, (p<0.05) followed by Bonferroni post-tests, (p<0.05) was used to assess significant leak of the TRITC-dextran of either tumor versus non-tumour tissue, and necrotic core versus non-tumour tissue at each timepoint. Timepoints that demonstrated significance are indicated by an asterisk.