监测双肿瘤荷瘤小鼠双重示踪剂微 PET 照射的早期反应。
Monitoring early responses to irradiation with dual-tracer micro-PET in dual-tumor bearing mice.
机构信息
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.
出版信息
World J Gastroenterol. 2010 Nov 21;16(43):5416-23. doi: 10.3748/wjg.v16.i43.5416.
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).
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).
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.
目的
使用（18）F-氟代胸苷（（18）F-FLT）和（18）F-氟代脱氧葡萄糖（（18）F-FDG）小动物正电子发射断层扫描（micro-PET）监测原发性和转移性结直肠癌（CRC）的早期放射反应。
方法
用 5、10 和 20 Gy 照射 SW480 和 SW620 原发性和转移性 CRC 细胞系。24 h 后，分析细胞周期阶段。通过将 SW480 和 SW620 细胞注射到小鼠中，建立原发性和转移性癌症的双重肿瘤荷瘤小鼠模型。在 5、10 和 20 Gy 照射前后进行（18）F-FLT 和（18）F-FDG 的 micro-PET。在肿瘤和背景上画出感兴趣区域（ROI），以计算组织中的肿瘤与非肿瘤（T/NT）比值。使用免疫组织化学检测和 Western blot 检测整合素β（3）、Ki-67、血管内皮生长因子受体 2（VEGFR2）和热休克蛋白 27（HSP27）的水平。
结果
SW480 和 SW620 细胞在 G（2）-M 期的比例随着辐射剂量的增加而降低。SW480 细胞在 G（0）-G（1）期的比例从 48.33%±4.55%增加到 87.09%±7.43%（P<0.001），SW620 细胞在 S 期的比例从 43.57%±2.65%增加到 66.59%±7.37%（P=0.021）。在 micro-PET 研究中，随着辐射剂量的增加，SW480 肿瘤中（18）F-FLT 的摄取从 3.65±0.51 显著减少到 2.87±0.47（P=0.008），SW620 肿瘤中从 2.22±0.42 减少到 1.76±0.45（P=0.026）。SW480 和 SW620 肿瘤中（18）F-FDG 的摄取减少但不显著（F=0.582，P=0.633 与 F=0.273，P=0.845）。辐射剂量与 SW480 和 SW620 肿瘤中（18）F-FLT 的摄取呈负相关（r=-0.727，P=0.004；和 r=-0.664，P=0.009）。在 SW480 或 SW620 肿瘤中，（18）F-FDG 摄取与辐射剂量之间未发现显著相关性。SW480 肿瘤中 HSP27 和整合素β（3）的表达高于 SW620 肿瘤。（18）F-FLT 摄取的 T/NT 比值与 HSP27 和整合素β（3）的表达呈正相关（r=0.924，P=0.004；和 r=0.813，P=0.025）。
结论
与（18）F-FDG 相比，（18）F-FLT 更适合监测原发性和转移性结直肠癌的早期放射反应。
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