Original Article
Copyright ©2010 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 21, 2010; 16(43): 5416-5423
Published online Nov 21, 2010. doi: 10.3748/wjg.v16.i43.5416
Monitoring early responses to irradiation with dual-tracer micro-PET in dual-tumor bearing mice
Hui Wang, Bo Liu, Jia-He Tian, Bai-Xuan Xu, Zhi-Wei Guan, Bao-Lin Qu, Chang-Bin Liu, Rui-Min Wang, Ying-Mao Chen, Jin-Ming Zhang
Hui Wang, Jia-He Tian, Bai-Xuan Xu, Zhi-Wei Guan, Chang-Bin 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
Author contributions: Wang H and Liu B contributed equally to this work; Wang H and Liu B performed the majority of experiments; Xu BX, Guan ZW, Liu CB, Wang RM collected all the PET imaging material; Chen YM, Zhang JM coordinated and provided vital reagents and analytical tools; Qu BL performed X-ray irradiation; Tian JH prepared and edited the manuscript.
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
Correspondence to: Jia-He Tian, Professor, Nuclear Medicine Department, The General Hospital of the Chinese People’s Liberation Army and Military Medical Postgraduate College, 28 Fuxing Road, Haidian District, Beijing 100853, China. tianjh@vip.sina.com.cn
Telephone: +86-10-66936429 Fax: +86-10-68161853
Received: June 7, 2010
Revised: August 2, 2010
Accepted: August 9, 2010
Published online: November 21, 2010
Abstract

AIM: To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with 18F-fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-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 SW480 and SW620 cells into mice. micro-PET with 18F-FLT and 18F-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 G2-M phase was decreased with an increasing radiation dose. The proportion of SW480 cells in the G0-G1 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, 18F-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. 18F-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 18F-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 18F-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 18F-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: 18F-FLT is more suitable than 18F-FDG in monitoring early responses to irradiation in both primary and metastatic lesions of colorectal cancer.

Keywords: 18F-fluorothymidine, 18F-fluorodeoxyglucose, Irradiation, Positron emission tomography, Colorectal cancer