Monitoring early responses to irradiation with dual-tracer micro-PET in dual-tumor bearing mice

AIM: To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with F-18-fluorothymidine (F-18-FLT) and F-18-fluorodeoxyglucose (F-18-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 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 5W480 and 5W620 cells into mice. micro-PET with F-18-FLT and F-18-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 beta(3), 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, F-18-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. F-18-FDG uptake in SW480 and 5W620 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 F-18-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 F-18-FDG uptake and radiation dose in SW480 or 5W620 tumors. HSP27 and integrin beta(3) expression was higher in SW480 than in SW620 tumors. The T/NT ratio for F-18-FLT uptake was positively correlated with HSP27 and integrin beta(3) expression (r = 0.924, P = 0.004; and r = 0.813, P = 0.025). CONCLUSION: F-18-FLT is more suitable than F-18-FDG in monitoring early responses to irradiation in both primary and metastatic lesions of colorectal cancer. (C) 2010 Baishideng. All rights reserved.