The parameters that limit supply of
photosensitizer to the
cancer cells in a solid
tumor were systematically analyzed with the use of microvascular transport modeling and histology data from frozen sections. In particular, the vascular permeability transport coefficient and the effective interstitial diffusion coefficient were quantified for
Verteporfin-for-Injection delivery of benzoporphyrin derivative (BPD). Orthotopic
tumors had higher permeability and diffusion coefficients (Pd = 0.036 microm/s and D = 1.6 microm(2)/s, respectively) as compared to subcutaneously grown
tumors (Pd = 0.025 microm/s and D = 0.9 microm2/s, respectively), likely due to the fact that the vessel patterns are more homogeneous orthotopically. In general, large intersubject and intratumor variability exist in the
verteporfin concentration, in the range of 25% in plasma concentration and in the range of 20% for tissue concentrations, predominantly due to these microregional variations in transport. However, the average individual uptake of
photosensitizer in
tumor tissue was only correlated to the total vascular area within the
tumor (R2 = 64.1%, P < 0.001). The data are consistent with a view that microregional variation in the vascular permeability and interstitial diffusion rate contribute the spatial heterogeneity observed in
verteporfin uptake, but that average supply to the tissue is limited by the total area of perfused blood vessels. This study presents a method to systematically analyze micro-heterogeneity as well as possible methods to increase delivery and homogeneity of
photosensitizer within
tumor tissue.