CAJ | 학술논문

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15 Gy X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;10 Gy照射后1、7及15 d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、15 Gy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、15 Gy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-FLT PET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15 d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-FLT PET有望用于监测食管癌照射后早期疗效.
목적 탐토18F-FLT재평개식관암세포급기동물모형경X선조사후조기생물학향응중적응용개치.방법 재체외이5、10화15 Gy X선분별조사인식관암세포Eca-109,조사전급조사후2、4화8h검측세포대 18F-FLT섭취솔적변화、세포상대존활솔화ATP적표체정황.장24지하식관암라서안수궤수자표법분성4조:대조(미조사)조;10 Gy조사후1、7급15 d각1조,분별행18F-FLT PET현상병측량종류대18F-FLT적섭취치(T/NT)적변화.현상후처사각조하류라서,취종류조직,용면역조직화학검측조사전、후류조직내세포증식핵항원(PCNA)급Ki67항원적표체.조간차이비교용단인소방차분석급량독립양본t검험,수거간상관성분석용Pearson직선상관분석.결과 조사전세포대18F-FLT섭취솔위(4.00±0.42)％;경5、10、15 Gy조사후2h분별하강지(3.65±0.41)％、(3.17±0.45)％화(2.53±0.28)％;조사후4h분별하강지(2.84±0.35)％、(2.58±0.39)％화(1.80±0.22)％;조사후8h분별하강지(2.71±0.23)％、(1.89±0.31)％화(1.44±0.20)％.여대조조비교,5、10、15 Gy조사후2、4、8h,세포상대존활솔차이무통계학의의(F=4.02,P＞0.05);ATP농도하강명현,정제량의뢰성.세포수조후적18F-FLT섭취솔여ATP농도정정상관(r=0.89,P＜0.01).18F-FLT PET현상시라서종류정고섭취,조사전T/NT위2.24±0.06,조사후1、7화15 d분별하강지1.99±0.09、1.85±0.04화1.15±0.10.류조직대18F-FLT적섭취치여PCNA、Ki67표체균정정상관(r=0.83화0.88,균P＜0.01).결론 18F-FLT재식관암세포급종류내섭취적변화능교호지평개기조사후조기생물학향응,18F-FLT PET유망용우감측식관암조사후조기료효.
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 18F-FLT and ATP levels(r =0.89,P＜0.01).18F-FLT 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.