부산대학교 도서관

Several recent reports have indicated that ionizing radiation enhances the metastatic growth of several human cancer cells, but the mechanisms for this phenomenon are not well elucidated.The purpose of this study is to evaluate the effectiveness of several molecular imaging modalities such as bioluminescence imaging (BLI) and 18F-FLT and 18F-FDG Positron Emission Tomography/Computed Tomography (PET/CT) in detecting the metastatic tumor and to analyze the gene expression profile to elucidate the mechanism of tumor metastasis after γ-IR in a tumor-bearing animal model.C6-L xenograft nude mousemodel were treated locally with γ-irradiation (γ-IR). Metastatic tumors after γ-IR were evaluated by BLI and PET/CT. Total mRNA from the cells of non-irradiated primary tumor (NRPT, n=5), γ-irradiated primary tumor (RPT, n=35), and the metastatic lung nodules (n=6) was isolated and analyzed by microarray. Metastatic lung nodules were detected by both BLI and PET/CT after 6-9 weeks of γ-IR in 6 (17.1%) of 35 mice. The images clearly demonstrated high BLI signal, [18F]FLT uptake and [18F]FDG uptake in themetastatic lung nodules. The mRNA microarray study shows up-regulation of cancer stem cell markers such as CD24 and CD44 and markers related to epithelial mesenchymal transition (EMT) in γ-IR tumors and down-regulation of those markers in the metastatic tumors. These findings support previous reports that well-known cancer stem cell markers such as CD24 and CD44 are correlated with γ-IR. In addition to these findings, the up-regulation of ALDH1A1 and ALDH3A1suggests the correlation of r-IR with repair response to hypoxic damage due to irradiation and gaining cancer stemness.Establishment of a murine metastasis model after γ-IR can help develop potential target therapeutic agent by identifying targets for biomarkers for tumor metastasis. Also molecular imaging would allow to improved identifying and understanding the molecular events occurring after IR.