摘要
AIM: To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with 18 Ffluorothymidine ( 18 F-FLT) and 18 F-fluorodeoxyglucose ( 18 F-FDG) small-animal position emission tomography (micro-PET). METHODS: The primary and metastatic CRC cell lines, SW480 and SW620, were irradiated with 5, 10 and 20, l l l , Gy. After 24 h, the cell cycle phases were analyzed. A dual-tumor-bearing mouse model of primary and metastatic cancer was established by injecting SW480 and SW620 cells into mice. micro-PET with 18 F-FLT and 18 F-FDG was performed before and 24 h after irradiation with 5, 10 and 20 Gy. The region of interest (ROI) was drawn over the tumor and background to calculate the ratio of tumor to non-tumor (T/NT) in tissues. Immunohistochemical assay and Western blotting were used to examine the levels of integrin β3, Ki-67, vascular endothelial growth factor receptor 2 (VEGFR2) and heat shock protein 27 (HSP27). RESULTS: The proportion of SW480 and SW620 cells in the G 2 -M phase was decreased with an increasing radiation dose. The proportion of SW480 cells in the G 0 -G 1 phase was increased from 48.33% ± 4.55% to 87.09% ± 7.43% (P < 0.001) and that of SW620 cells in the S-phase was elevated from 43.57% ± 2.65% to 66.59% ± 7.37% (P = 0.021). In micro-PET study, with increasing dose of radiation, 18 F-FLT uptake was significantly reduced from 3.65 ± 0.51 to 2.87 ± 0.47 (P = 0.008) in SW480 tumors and from 2.22 ± 0.42 to 1.76 ± 0.45 (P = 0.026) in SW620 tumors. 18 F-FDG uptake in SW480 and SW620 tumors was reduced but not significantly (F = 0.582, P = 0.633 vs F = 0.273, P = 0.845). Dose of radiation was negatively correlated with 18 F-FLT uptake in both SW480 and SW620 tumors (r = -0.727, P = 0.004; and r = -0.664, P = 0.009). No significant correlation was found between 18 F-FDG uptake and radiation dose in SW480 or SW620 tumors. HSP27 and integrin β3 expression was higher in SW480 than in SW620 tumors. The T/NT ratio for 18 F-FLT uptake was positively correlated with HSP27 and integrin β3 expression (r = 0.924, P = 0.004; and r = 0.813, P = 0.025). CONCLUSION: 18 F-FLT is more suitable than 18 F-FDG in monitoring early responses to irradiation in both primary and metastatic lesions of colorectal cancer.
AIM: To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with 18 Ffluorothymidine ( 18 F-FLT) and 18 F-fluorodeoxyglucose ( 18 F-FDG) small-animal position emission tomography (micro-PET). METHODS: The primary and metastatic CRC cell lines, SW480 and SW620, were irradiated with 5, 10 and 20, l l l , Gy. After 24 h, the cell cycle phases were analyzed. A dual-tumor-bearing mouse model of primary and metastatic cancer was established by injecting SW480 and SW620 cells into mice. micro-PET with 18 F-FLT and 18 F-FDG was performed before and 24 h after irradiation with 5, 10 and 20 Gy. The region of interest (ROI) was drawn over the tumor and background to calculate the ratio of tumor to non-tumor (T/NT) in tissues. Immunohistochemical assay and Western blotting were used to examine the levels of integrin β3, Ki-67, vascular endothelial growth factor receptor 2 (VEGFR2) and heat shock protein 27 (HSP27). RESULTS: The proportion of SW480 and SW620 cells in the G 2 -M phase was decreased with an increasing radiation dose. The proportion of SW480 cells in the G 0 -G 1 phase was increased from 48.33% ± 4.55% to 87.09% ± 7.43% (P < 0.001) and that of SW620 cells in the S-phase was elevated from 43.57% ± 2.65% to 66.59% ± 7.37% (P = 0.021). In micro-PET study, with increasing dose of radiation, 18 F-FLT uptake was significantly reduced from 3.65 ± 0.51 to 2.87 ± 0.47 (P = 0.008) in SW480 tumors and from 2.22 ± 0.42 to 1.76 ± 0.45 (P = 0.026) in SW620 tumors. 18 F-FDG uptake in SW480 and SW620 tumors was reduced but not significantly (F = 0.582, P = 0.633 vs F = 0.273, P = 0.845). Dose of radiation was negatively correlated with 18 F-FLT uptake in both SW480 and SW620 tumors (r = -0.727, P = 0.004; and r = -0.664, P = 0.009). No significant correlation was found between 18 F-FDG uptake and radiation dose in SW480 or SW620 tumors. HSP27 and integrin β3 expression was higher in SW480 than in SW620 tumors. The T/NT ratio for 18 F-FLT uptake was positively correlated with HSP27 and integrin β3 expression (r = 0.924, P = 0.004; and r = 0.813, P = 0.025). CONCLUSION: 18 F-FLT is more suitable than 18 F-FDG in monitoring early responses to irradiation in both primary and metastatic lesions of colorectal cancer.
作者
Hui Wang, Jia-He Tian, Bai-Xuan Xu, Zhi-Wei Guan, ChangBin Liu, Rui-Min Wang, Ying-Mao Chen, Jin-Ming Zhang, Nuclear Medicine Department, The General Hospital of the Chinese People’s Liberation Army and Military Medical Postgraduate College, Beijing 100853, China Bo Liu, Department of Hepatobiliary Surgery, The General Hospital of the Chinese People’s Liberation Army and Military Medical Postgraduate College, Beijing 100853, China Bao-Lin Qu, Department of Radiation Oncology, The General Hospital of the Chinese People’s Liberation Army and Military Medical Postgraduate College, Beijing 100853, China
基金
Supported by Grants from the China Postdoctoral Science Foundation, No. 20070420569
the Special Fund, China Postdoctoral Science Foundation No. 200902679
the National Natural Science Foundation of China No. 30770607