Spectral imaging of microvascular function in a renal cell carcinomaafter treatment with a vascular disrupting agent

摘要

Tumors are highly metabolically active and thus require ample oxygen and nutrients to proliferate. Neovasculature generated by angiogenesis is required for tumors to grow beyond a size of about 1-2mm. Functional tumor vasculature also provides an access point for development of distant metastases. Due to the importance of the microvasculature for tumor growth, proliferation, and metastasis, the microvasculature has emerged as a therapeutic target for treatment of solid tumors. We employed spectral imaging in a rodent window chamber model to observe and measure the oxygen transport function of tumor microvasculature in a human renal cell carcinoma after treatment with a fast acting vascular disrupting agent. Human Caki-1 cells were grown in a dorsal skin-fold window chamber in athymic nude mice. Spectral imaging was used to measure hemoglobin saturation immediately before, immediately after and also at 2, 4, 6, 8, 24 and 48 hours after administration of the tubulin binding agent OXi4503. Up to 4 hours after treatment, tumor microvasculature was disrupted from the tumor core towards the periphery as seen in deoxygenation as well as structural changes of the vasculature. Reoxygenation and neovascularization commenced from the periphery towards the core from 6 - 48 hours after treatment. The timing of the effects of vascular disrupting agents can influence scheduling of repeat treatments and combinatorial treatments such as chemotherapy and radiation therapy. Spectral imaging can potentially provide this information in certain laboratory models from endogenous signals with microvessel resolution.