^(11)C-PD153035摄取与肿瘤EGFR表达水平相关性的研究

The uptake of ^(11)C-PD153035 correlated with the EGFR expression in experimental tumors

目的研究^(11)C-4-(3-溴苯氨基)-6,7-双甲氧喹唑啉(PD153035)摄取与表皮生长因子受体(EGFR)表达水平之间的关系。方法在体外测定人乳腺癌细胞 MDA-MB-468、MDA-MB-231和人肺腺癌细胞 A549的 EGFR 表达水平以及对^(11)C-PD153035的摄取。分别建立裸鼠种植瘤模型,通过尾静脉注射^(11)C-PD153035后即刻行 PET 显像,用感兴趣区(ROI)法在注射后即刻及10,20,30,40,50和60 min 测定病灶/健侧前肢正常组织放射性计数(T/NT)比值。显像结束后立即处死动物,切除肿瘤,测量肿瘤内摄取的放射性。结果在体外肿瘤细胞对^(11)C-PD153035的摄取与肿瘤细胞 EGFR 表达水平明显相关(r^2=0.78,P=0.001)。在动物体内,T/NT 与肿瘤细胞的 EGFR 表达水平明显相关(r^2=0.65,P=0.004)。离体肿瘤组织对^(11)C-PD153035的摄取与肿瘤细胞的 EGFR 表达水平明显相关(r^2=0.64,P=0.005)。结论 ^(11)C-PD153035的摄取与肿瘤细胞的 EGFR 表达水平明显相关,EGFR 的^(11)C-PD153035 PET 显像有可能为肿瘤的诊断与治疗提供依据。

Objective The accumulation of a new PET tracer, ^11C-4-（3-bromoanilino）-6,7-dimethoxyquinazoline （PD153035）, was found related to the expression level of epidermal growth factor receptor （EGFR） in tumor tissues. The aim of the study was to explore the potential of the tracer for PET imaging. Methods The relationship of cellular uptake of ^11C-PD153035 and the EGFR expression was detected in vitro in MDA-MB-468, A-549 and MDA-MB-231 cell lines. PET imaging was carried out in 9 tumor-bearing mice, 3 for each cell-line, at 0,5 , 10,20,30,40,50 and 60 min post ^11C-PD153035 injection. The uptake ratio of tumor to non-tumor （T/NT） was calculated using region of interest （ROI） method, and then the nude mice were sacrificed with tumors excised. The ex vivo ^11C-PD153035 accumulation and the EGFR expression of different tumors were detected, respectively. Results Both in vitro and ex vivo studies proved that the accumulation of ^11C-PD153035 closely correlated with the EGFR expression of the tumor cells （r^2= 0. 78, P = 0. 001 ; r^2 = 0.64, P = 0. 005 ）. The T/NT ratio was observed correlated to EGFR （ r^2 = 0. 65, P = 0.004） too. Conclusion This study showed that the uptake of n C-PD153035 closely correlated with EGFR expression, and of potential for both diagnostic and therapy-monitoring applications.