^18F-FDG、^18F-FLT细胞结合评价肺腺癌5-Fu化疗早期反应的细胞学研究

An Experimental Study on the Early Changes in ^18F-FDG and ^18F-FLT Uptake on Human Lung Adenocarcinoma A-549 Cells after Chemotherapy of 5-Fu

目的：通过测定^18F-氟代葡萄糖（FDG）和^18F-氟代胸苷（FLT）细胞结合率的变化来评估不同浓度氟尿嘧啶（5-Fu）对肺腺癌A-549细胞化疗早期反应的疗效并对两种显像剂进行初步比较。方法不同浓度（0.125、0.25、0.5、1.0 mg/mL）5-Fu 1.0 mL分别与肺腺癌A-549细胞共同孵育24 h、48 h，测定细胞对^18F-FDG和^18F-FLT的细胞结合变化并与MTT法测定的存活细胞数目和细胞抑制率比较。结果（1）5-Fu作用24 h和48 h后，^18F-FDG和^18F-FLT细胞结合率均随药物浓度的增加而下降，两者与药物浓度均呈负相关（24 h：^18F-FLT r=-0.950，P＜0.01，^18F-FDG r=-0.844，P＜0.01；48 h：^18F-FLT r=-0.939，P＜0.01，^18F-FDG r=-0.786，P＜0.01）；48 h与24 h相比，两种显像剂细胞摄取率均降低；（2）24 h和48 h MTT细胞抑制率与^18F-FDG和^18F-FLT细胞结合抑制率均呈正相关（24 h：^18F-FLT r=0.897，P＜0.01，^18F-FDG r=0.978，P＜0.05；48 h：^18F-FLT r=0.876，P＜0.01，^18F-FDG r=0.910，P＜0.01）；（3）^18F-FDG细胞结合抑制率与^18F-FLT细胞结合抑制率呈正相关（24h：r=0.657，P＜0.01；48 h：r=0.432，P＜0.05）。结论（1）^18F-FDG和^18F-FLT摄取变化可以早期评价5-Fu对肺腺癌A-549细胞的化疗疗效；随着5-Fu化疗时间的延长，肺腺癌A-549细胞摄取率下降更明显；（2）^18F-FDG和^18F-FLT相比，^18F-FDG细胞结合抑制率与^18F-FLT细胞结合抑制率呈正相关，且24 h较48 h相关性高；^18F-FLT早期摄取率与药物浓度的关系更密切，下降趋势更加明显，与MTT的关系更显著。因此，^18F-FLT联合^18F-FDG用于评价化疗疗效和指导用药将成为一种新的思路。

Objective To evaluate the effect of different concentrations of 5-Fu early by uptake of ^18F-FDG and ^18F-FLT in human lung adenocarcinoma A-549 cells. At the same time, to compare the two kinds of imaging agents preliminarily. Methods The proliferation inhibition effect by MTT and the uptake rates of ^18F-FDG and ^18F-FLT were detected after treatment with 5-Fu at 24 h and 48 h. Results （1）The uptake rates were negatively cor-related with the doses of 5-Fu at 24 h and 48 h after administration of 0.125, 0.25, 0.5 and 1.0 mg/mL 5-Fu （24 h：^18F-FLT r=-0.950, P〈0.01, ^18F-FDG r=-0.844, P〈0.01, 48 h： ^18F-FLT r=-0.939, P〈0.01, ^18F-FDG r=-0.786, P〈0.01） and the uptake rates of ^18F-FDG and ^18F-FLT with A-549 cells were lower at 48 h after administration of 5-Fu than at 24 h. （2）The binding inhibition efifciency was positively correlated with the proliferation inhibition （24 h： ^18F-FLT r=0.897, P〈0.01, ^18F-FDG r=0.978, P〈0.05, 48 h： ^18F-FLT r=0.876, P〈0.01, ^18F-FDG r=0.910,P〈0.01）. （3）The binding inhibition efifciency of the two kinds of agents were correlated （24 h：r=0.657, P〈0.01, 48 h：r=0.432, P〈0.05）. Conclusion （1）The study indicated that early therapeutic effect of 5-Fu for human lung adenocarcinoma A-549 cells could be assessed by ^18F-FDG and ^18F-FLT. （2）The binding efifciency of ^18F-FDG was more positive correlated with ^18F-FLT at 24 h than at 48 h. The relationship between early uptake rates and drug concentrations of ^18F-FLT were more closely, more pronounced downward and more signiifcantly correlated with MTT. Therefore, ^18F-FLT combined with ^18F-FDG could be used to evaluate the curative effect of chemotherapy and medication guide which will become a new way of thinking.