Abstract
Abstract [Purpose] Tumor microenvironment is characterized by the conditions including hypoxia, low nutrition, stromal cell infiltration, and acidosis due to incomplete blood vessel network. Tumor microenvironment has been recognized as a major factor influencing not only the response to anti-cancer therapies but also malignant progression and metastasis. Non-invasive imaging of such a microenvironment by positron emission tomography (PET) will provide more therapeutic merits. Accumulation of FDG, 2-deoxy-2-[F-18]fluoro-D-glucose, a most-often used PET probe, in tumor has been reported to correlate with the metastasis and malignancy. However, the FDG uptake profile in the microenvironment has remained unknown. In this study, we simultaneously visualized the intratumoral FDG distribution and the microenvironment by using microautoradiography in microscopic spatial resolution combined with immunohistochemistry. [Methods] Human epidermoid carcinoma cell line A431 was transplanted into the back of female SCID mice, and FDG was injected into the mice 2 weeks after the transplantation. The tumors were removed from mice 45 minutes after the FDG administration and the frozen sections were obtained. Overall image of the intratumoral FDG distribution was obtained by conventional autoradiography. FDG distribution and microenvironment in microscopic levels were visualized by microautoradiography followed by immunohistochemical detection of hypoxic condition and cell-specific markers. [Result & Conclusion] Conventional autoradiography and microautoradiography showed the similar pattern in FDG distribution in the tumor. Furthermore, microautoradiographic study with immunohistochemistry revealed that grains at high-density were observed in pimonidazol (hypoxia marker)-accumulated areas showing infiltration of many S100A4-immunopositive fibroblasts. These results suggested that FDG accumulation was prominent in stromal cells involved in hypoxic condition in tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2436. doi:1538-7445.AM2012-2436
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