Aim
To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with (18)F-fluorothymidine ((18)F-FLT) and (18)F-fluorodeoxyglucose ((18)F-FDG) small-animal position emission tomography (micro-PET).
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.
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 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 β(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, (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 β(3) 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 β(3) expression (r = 0.924, P = 0.004; and r = 0.813, P = 0.025).