P-糖蛋白对荷瘤裸鼠体内摄取18F-FDG的影响

The effect of P-glycoprotein on 18F-FDG uptake in tumor-bearing nude mice

目的 研究Bcap37及Bcap37/MDR1荷瘤裸鼠在依克立达（GH20918）干预前后的18F-FDG摄取变化,在活体内评价P-gp对18F-FDG摄取的影响.方法 分别用人乳腺癌Bcap37细胞及转MDR1基因的Bcap37（Bcap37/MDR1）细胞建立荷瘤裸鼠模型.荷瘤裸鼠培F-FDG microPET动态采集：10只荷瘤裸鼠（Bcap37及Bcap37/MDR1荷瘤裸鼠各5只）经尾静脉给予7.4 MBq 18F-FDG,给药后立即采集,共采集90 min,得到各个时间段的动态显像图,绘制ROI的TAC.隔日相同采集及处理方法,尾静脉给予含GF120918（按体质量2.0 mg/kg）的18F-FDG 7.4 MBq,获得GF120918干预后肿瘤组织18F-FDG摄取的TAC,观察GF120918干预前后TAC的变化.另取10只荷瘤裸鼠（Bcap37及Bcap37/MDR1荷瘤裸鼠各5只）,行18F-FDG microPET静态显像,并比较GF120918干预前后肿瘤组织的SUV mean的变化.数据分析采用两样本t检验.结果 Bcap37荷瘤裸鼠肿瘤组织在GF120918干预前后的TAC差异元统计学意义,GF120918可明显增加Bcap37/MDR1荷瘤裸鼠肿瘤组织平台期18F-FDG的摄取水平.荷瘤裸鼠静态microPET显像示,GF120918干预前后Bcap37及Bcap37/MDR1荷瘤裸鼠肿瘤组织的SUVmean分别为1.028±0.045、1.052±0.028和0.712±0.031、1.015±0.043,前者干预前后的SUVmean差异无统计学意义（t=1.792,P＞0.05）,后者干预前后的SUVmean差异有统计学意义（t=3.365,P＜0.05）.在无GF120918存在情况下,Bcap37荷瘤裸鼠肿瘤组织的18 F-FDG摄取要高于Bcap37/MDR1荷瘤裸鼠（t=3.952,P＜0.05）;在给予GF120918后,两者间18F-FDG摄取水平差异无统计学意义（t=1.835,P＞0.05）.结论 18F-FDG是P-gp的底物之一,18F-FDG联合GF120918可能是一种有效、无创检测肿瘤MDR的方法.

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice （1＆#215; 107cells/ml,0.2 ml/mouse） to construct mice models.Bcap37 （n=5） or Bcap37/MDR1 （n=5） tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar （GF120918） and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake （SUV） in Bcap37 tumors （1.052±0.028,1.028±0.045,t =1.792,P〉0.05）,but significantly increased the SUV in Bcap37/MDR1 tumors （1.015±0.043,0.712±0.031,t=3.365,P〈0.05）;The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 （t =3.952,P〈0.05）.The SUV was not significantly different when GF120118 was injected （t=1.835,P〉0.05）.Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor＆#39;s MDR.