摘要目的 评价18F-脱氧胸腺嘧啶核苷(FLT)监测结肠癌细胞早期放射反应的作用.方法 应用四甲基偶氮唑蓝(MTT)检测并绘制SW480细胞受X线照射后生长曲线,光学显微镜下观察细胞形态变化.流式细胞仪检测照射后肿瘤细胞增殖周期的重新分布.分别于体外细胞以及肿瘤内检测照射前、后细胞摄取18F-FLT的变化.将18F-FLT(0.05±0.01)MBq加入培养液孵育细胞,分别于30,60,90,120 min测定细胞摄取18F-FLT的放射性.经荷瘤裸鼠尾静脉注射18F-FLT(1.90±0.85)MBq(0.25 ml),60 min后处死动物,切除肿瘤与肌肉、肺、肝等,测定肿瘤与其他脏器摄取放射性比值变化.应用单因素方差分析进行统计学处理.结果 X线照射后,SW480细胞增殖受到明显的抑制,呈剂量依赖性.细胞形态随照射剂量的不同发生不同的变化.照射后细胞周期发生重新分布.10 Gy组,S期细胞百分比24 h从33.23%降至15.19%,72 h后降至12.44%.20 Gy组,S期细胞百分比24 h后从33.23%降至9.24%,72 h后降至5.43%.体外摄取实验发现,注射后60 min,SW480细胞摄取18F-FLT百分比为(5.21±1.60)%,10 Gy照射24 h后下降至(4.27±0.48)%,72 h降至(3.39±0.59)%.20 Gy组:照射后24 h,SW480摄取的放射性百分比下降至(3.41±0.58)%,72 h后降至(1.63±0.49)%.两照射组在72 h内分别下降了34.94%,69.72%(24 h∶F=8.253,P=0.009;72 h∶F=36.715,P＜0.001).单位质量肿瘤组织摄取的18F-FLT随照射剂量的增加而逐渐降低(10Gy组:F=12.388,P=0.007;20 Gy组:F=16.744,P=0.004).结论 18F-FLT在结肠癌细胞内的摄取可以快速反映照射治疗后的细胞变化,18F-FLT可能用于检测结肠癌放射治疗早期反应.

abstractsObjective To evaluate whether 18F-fluorothymidine(FLT) can be used to monitor early response to irradiation in colorectal cancer (CRC).Methods SW480 cells were cultured and irradiated with 0, 10, and 20 Gy.Twenty-four hours later, morphological changes, apoptosis, necrosis, proliferation,and cell cycle phases were observed.Uptake of 18F-FLT was measured in these tumors in vitro from 24 h to 72 h after irradiation.The one-way analysis of variance was used to analyze the data.Results Apoptotic and necrotic cells were detected 24 h after radiotherapy.SW480 cells proliferation was significantly delayed after irradiation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTI) assay.Cell cycle analysis showed that SW480 cells had a decreased fraction of cells in S phase( from 33.23% to 9.24%,then to 5.43% ) and an arrested fraction in G0-G1.After SW480 cells were cultured for60 min, the uptake of 18F-FLT was (5.21 ± 1.60) %; and 24 h after irradiation of 10 Gy, the uptake decreased significantly to (4.27±0.48)% (F=8.253, P=0.009).And 72 h after irradiation, the uptake further decreased significantly to (3.39 ± 0.59) % ( F = 36.715, P＜0.001 ).In tumor tissue, the uptake of 18F-FLT reduced significantly 72 h after radiotherapy (10 Gy:F = 12.388, P = 0.007; 20 Gy:F = 16.744, P = 0.004) and the attenuation degree increased with the radiation dose.Conclusion The uptake of 18F-FLT in SW480 cells or in CRC could reflect the changes of SW480 cells in proliferation, cell cycle re-distribution, cell apoptosis and necrosis.The results suggest that 18F-FLT may be used for monitoring early response to irradiation of CRC.