title: Monitoring early responses to irradiation with dual-tracer micro-PET in dual-tumor bearing mice.
abstract: OBJECTIVE
  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).
  
  
  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).
  
  
  CONCLUSIONS
  (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.
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Tian
authors.forename: Bai-Xuan
authors.initials: BX
authors.lastname: Xu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Guan
authors.forename: Bao-Lin
authors.initials: BL
authors.lastname: Qu
authors.forename: Chang-Bin
authors.initials: CB
authors.lastname: Liu
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Wang
authors.forename: Ying-Mao
authors.initials: YM
authors.lastname: Chen
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000532:radiotherapy*; D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000532:radiotherapy*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D019788:Fluorodeoxyglucose F18; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008991:Monitoring, Physiologic; D049268:Positron-Emission Tomography; D011878:Radiotherapy; D014183:Transplantation, Heterologous
chemical_list: D019788:Fluorodeoxyglucose F18