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27 February 2007 Tumor vascular volume determines photosensitizer uptake in MATLyLu prostate tumor model
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Abstract
The parameters which limit supply of photosensitizer to the cancer cells in a solid tumor were systematically analyzed using 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 a higher permeability and diffusion coefficients (Pd= 0.036 &mgr;m/s and D = 1.6 &mgr;m2/s, respectively) as compared to subcutaneously grown tumors (Pd = 0.025 &mgr;m/s and D = 0.9 &mgr;m2/s, respectively), likely due to the fact that the vessel patterns are more homogeneous orthotopically. In general, large inter-subject and intra-tumor 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 micro-regional 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 is consistent with a view that micro-regional variation in the vascular permeability, interstitial diffusion rate, all contributes 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 microheterogeneity as well as possible methods to increase delivery and homogeneity of photosensitizer within tumor tissue.
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Xiaodong Zhou, Bin Chen, P. Jack Hoopes, Tayyaba Hasan, and Brian W. Pogue "Tumor vascular volume determines photosensitizer uptake in MATLyLu prostate tumor model", Proc. SPIE 6427, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVI, 64270S (27 February 2007); https://doi.org/10.1117/12.699033
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