^18F-FLT评价食管癌照射后早期生物学响应的实验研究

目的探讨^18F—FLT在评价食管癌细胞及其动物模型经X线照射后早期生物学响应中的应用价值。方法在体外以5、10和15Gyx线分别照射人食管癌细胞Eca-109，照射前及照射后2、4和8h检测细胞对^18F—FLT摄取率的变化、细胞相对存活率和ATP的表达情况。将24只荷食管癌裸鼠按随机数字表法分成4组：对照（未照射）组；10Gy照射后1、7及15d各1组，分别行^18F—FLT PET显像并测量肿瘤对^18F—FLT的摄取值（T／NT）的变化。显像后处死各组荷瘤裸鼠，取肿瘤组织，用免疫组织化学检测照射前、后瘤组织内细胞增殖核抗原（PCNA）及Ki67抗原的表达。组间差异比较用单因素方差分析及两独立样本t检验，数据间相关性分析用Pearson直线相关分析。结果照射前细胞对^18F-FLT摄取率为（4．00±0．42）％；经5、10、15Gy照射后2h分别下降至（3．65±0．41）％、（3．17±0．45）％和（2．53±0．28）％；照射后4h分别下降至（2．84±0．35）％、（2．58±0．39）％和（1．80±0．22）％；照射后8h分别下降至（2．71±0．23）％、（1．89±0．31）％和（1．44±0．20）％。与对照组比较，5、10、15q照射后2、4、8h，细胞相对存活率差异无统计学意义（F=4．02，P〉0．05）；ATP浓度下降明显，呈剂量依赖性。细胞受照后的^18F—FLT摄取率与ATP浓度呈正相关（r=0．89，P〈0．01）。^18F—FLTPET显像示裸鼠肿瘤呈高摄取，照射前T／NT为2．24±0．06，照射后1、7和15d分别下降至1．99±0．09、1．85±0．04和1．15±0．10。瘤组织对^18F-FLT的摄取值与PCNA、Ki67表达均呈正相关（r=0．83和0．88，均P〈0．01）。结论^18F—FLT在食管癌细胞及肿瘤内摄取的变化能较好地评价其照射后早期生物学响应，^18F—FLTPET有望用于监测食管癌照射后早期疗效。

The experimental study of ^18F-FLT in monitoring the early biologic response of esophageal carcinoma to irradiation

Objective To explore the value of ^18F-FLT in monitoring the early response of esophageal carcinoma cells and tumor model to irradiation. Methods After 2, 4 and 8 h of irradiation with different doses （5, 10, 15 Gy） in vitro, the uptake ratio of ^18F-FLT and the relative survival rate and ATP levels in esophageal carcinoma （Eca）-109 cells were measured. Twenty-four BALB/c nu/nu mice bearing esophageal carcinoma were divided into 4 groups by random number table method. Three groups were treated with 10 Gy X-ray irradiation and the other group was control group （0 Gy）. Tumor uptake of ^18F-FLT（T/NT） was calculated before （control group ）and on the 1st, 7th, 15th d after irradiation（ 3 treated groups）. The mice were sacrificed after imaging and the expressions of proliferating cell nuclear antigen （ PCNA ） and Ki67 were detected. One-way analysis of variance, two-sample t test and Pearson correlation were applied for statistical analysis. Results The uptake ratio of ^18F-FLT in Eca-109 cells before irradiation was （4.00± 0.42） %. After irradiation with 5, 10, 15 Gy, the uptake ratios decreased to （ 3.65±0.41 ） %, （ 3.17±0.45）% and （2.53±0.28）% at 2 h, （2.84±0.35）%, （2.58±0.39）% and （1.80±0.22）% at 4 h, （2.71±0. 23）%, （1.89±0.31）% and （1.44±0.20）% at 8 h, respectively. The relative survival rates of Eca-109 cells after 2, 4 and 8 h of irradiation with different doses （5, 10, 15 Gy） were not significantly different （ F= 4. 02, P〉0.05）. There was a significant correlation between 18 F-FLT and ATP levels（ r = 0.89, P〈0.01 ）. ^18FFLT PET imaging showed the tumor had a high uptake. The ratio in xenografts was 2.24±0.06 before irradiation. It decreased to 1.99±0.09,1.85±0.04 and 1.15±0.10 on the 1st, 7th, 15th d after irradiation. Tumor uptake of ^18F-FLT was closely correlated with PCNA and Ki67 expression （r= 0.83, 0.88, both P〈0.01）. Conclusions The uptake changes of ^18F-FLT in the esophageal carcinoma cells and tumor tissues may reflect the early biological response of esophageal carcinoma to irradiation, ^18F-FLT PET may be used to monitor the early response of esophageal carcinoma to irradiation.