Physiologic, hemodynamic and morphologic changes of tumor vasculature are complex and heterogeneous among various regions of a tumor and among various tumor types. This is due to the heterogeneity of the morphology of the tumor vessels, changes in rheologic property of the blood components, and changes in the interstitial pressure of the surrounding stroma. The widely accepted standard for quantification of angiogenesis is intratumoral vessel count. However, vessel count is limited by: 1) random sampling of biopsy specimen; and 2) tissue biopsy requirement, which is invasive and not practical for monitoring the changes after treatment. Non-invasive quantification of these changes in the tumor vasculature, in addition to vessel count would provide novel and essential methods to monitor the effects of the treatment, and particularly, antiangiogenic therapy.
Specific aims are as tallows: 1. To quantify tumor blood flow, tumor blood volume, mean transit time, and capillary permeability using high-resolution, multislice CT following rapid bolus of IV contrast enhancement in tumor models in mice. We will use the mathematical model developed by T-Y Lee (collaborator) to quantify the above parameters and compare them with vessel counts. 2. To quantify the effects of antiangiogenic therapy on tumor blood flow, tumor blood volume, mean transit time, and capillary permeability fraction by using CT tumor perfusion in mice. CT scan will be used to examine the antiangiogenic effect of SU-6668. The changes in the above parameters will be compared with vessel counts and tumor cell apoptosis as determined by immunohistochemistry. If we are successful in correlating the parameters of tumor perfusion with vessel counts, this developmental project can be expanded to a full project to quantify the effects of various antiangiogenic agents and correlate the changes with the biologic effects of those agents. The technique has the potential for use during in situ monitoring of antiangiogenic therapy in clinical trials.
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