In-vivo visualization of tumor microvessel density and response to anti-angiogenic treatment by high resolution MRI in mice

利用高分辨率磁共振成像技术在小鼠体内可视化肿瘤微血管密度及对抗血管生成治疗的反应

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作者:Roland T Ullrich,Jan F Jikeli, Michael Diedenhofen, Philipp Böhm-Sturm, Maike Unruh, Stefan Vollmar, Mathias Hoehn

Abstract

Purpose: Inhibition of angiogenesis has shown clinical success in patients with cancer. Thus, imaging approaches that allow for the identification of angiogenic tumors and the detection of response to anti-angiogenic treatment are of high clinical relevance. Experimental design: We established an in vivo magnetic resonance imaging (MRI) approach that allows us to simultaneously image tumor microvessel density and tumor vessel size in a NSCLC model in mice. Results: Using microvessel density imaging we demonstrated an increase in microvessel density within 8 days after tumor implantation, while tumor vessel size decreased indicating a switch from macro- to microvessels during tumor growth. Moreover, we could monitor in vivo inhibition of angiogenesis induced by the angiogenesis inhibitor PTK787, resulting in a decrease of microvessel density and a slight increase in tumor vessel size. Conclusions: We present an in vivo imaging approach that allows us to monitor both tumor microvessel density and tumor vessel size in the tumor. Moreover, this approach enables us to assess, early-on, treatment effects on tumor microvessel density as well as on tumor vessel size. Thus, this imaging-based strategy of validating anti-angiogenic treatment effects has high potential in applications to preclinical and clinical trials.

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