摘要目的 评价PET在预测结肠癌转移特性中的作用.方法 体外培养人结肠癌SW480、SW620细胞并分别种植裸鼠,形成移植瘤,观察肿瘤生长、转移情况以及生存期.分别于体内、体外检测肿瘤细胞对18F-脱氧葡萄糖(FDG)、18F-脱氧胸腺嘧啶核苷(FLT)的摄取.在体外分别于30,60,90和120 min测定肿瘤细胞摄取18F-FDG与18F-FLT的放射性.经鼠尾静脉注射18F-FDG、18F-FLT,60 min后行动物PET显像,利用感兴趣区(ROI)计算肿瘤/正常组织放射性(T/NT)比值.应用免疫细胞化学染色与Western blot法检测细胞以及肿瘤组织热休克蛋白27(HSP27)、整合素β3(Integrinβ3)、血管内皮生长因子受体2(VEGFR2)、核增殖抗原(Ki67)蛋白表达.应用独立样本t检验、Fisher精确检验以及直线回归分析研究体内外放射性摄取的差异以及放射性摄取与肿瘤标志物表达之间的关系.结果 SW480移植瘤较SW620肿瘤成瘤早、生长快、生存期短、肝肺转移率高.体外摄取实验示,18F-FDG在SW480与SW620细胞中的摄取60 min时分别达到(1.76±0.87)%和(1.14±0.38)%(t=-2.507,P=0.021);18F-FLT分别达到(5.21±1.60)%和(2.90±1.82)%(t=3.497,P=0.002).SW480较SW620细胞摄取18F-FDG、18F-FLT高,18F-FLT在细胞内的摄取高于18F-FDG.动物PET显像示,18F-FDG在SW480与SW620肿瘤中的T/NT比值分别为2.69±0.98,3.09±1.26(t=0.657,P=0.524);18F-FLT T/NT比值分别为3.65±0.51,2.22±0.42(t=6.491,P＜0.001);18F-FLT摄取与肿瘤组织内HSP27表达(r=0.924,P=0.004)、Integrnβ3表达(r=0.813,P=0.025)呈明显正相关.而18F-FDG的摄取与荷瘤鼠的生存期呈明显负相关(r=-0.500,P=0.017).结论 18F-FDG、18F-FLT PET在肿瘤内的摄取可反映结肠癌不同的生物学行为,18F-FLT在结肠癌内的高摄取可预测结肠癌具有高转移潜能.

abstractsObjective To evaluate the predictive value of 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine(FLT) PET in monitoring the metastatic potential of human colorectal cancer (CRC).Methods Human CRC cell lines SW480 and SW620 were cultured and implanted into nude mice to create CRC models. Tumor growth,metastatic status and survival were assessed in CRC bearing mice. Uptake of 18F-FDG and 18F-FLT in SW480 and SW620 cells was detected In vitro at 0,30,60,90,120 min after incubation. PET images of both tracers were acquired for SW480 and SW620 tumor-bearing mice using the small animal PET at 60 min after tracer injection. Region of interest (ROI) was drawn using Image J software on reconstructed PET images. Immunocytochemistry and Western blot analysis of the tumor tissue were performed. The correlation between tracer uptake and tumor marker expression was evaluated using linear regression. Results Compared with SW620 tumor-bearing mice,SW480 induced tumor grew much faster ( t = - 3.332,P = 0.004),the tumor-bearing mice had more serious dyscrasia ( t = 2.240,P = 0.038 ),shorter survival and higher metastatic rate. In vitro study,the uptake of both 18F-FDG and 18F-FLT in SW620 cells was lower than that in SW480 cells. 18F-FLT uptake was higher than 18F-FDG uptake in both SW480 and SW620 cells. After incubation for 60 min,the uptake of 18F-FDG in SW480 and SW620 cells was ( 1.76 ± 0.87 )% and ( 1.14 ± 0.38 )%,respectively ( t = - 2.507,P = 0.021 ); while the uptake of 18F-FLT in SW480 and SW620 cells was (5.21 ± 1.60)% and (2.90 ± 1.82)%,respectively (t =3.497,P =0.002). In micro-PET study,the 18F-FDG radioactivity ratio of tumor to non-tumor (T/NT) in SW480 and SW620 tumors was 2.69 ± 0.98 and 3.09 ± 1.26 respectively (t =0.657,P =0.524); while T/NT of 18F-FLT in SW480 and SW620 tumors was 3.65 ±0.51 and 2.22 ±0.42 (t =6.491,P ＜0.001 ),respectively. In immunocytochemistry and western blot assay,heat shock protein(HSP) 27,Integrin β3,vascular endothelial growth factor receptor 2 ( VEGFR2 ) and Ki67 were all over expressed in two kinds of tumor cells with different intensities. HSP27 and Integrin β3 expression was higher in SW480 cells than that in SW620 cells. While VEGFR and Ki67 expression was lower in SW480 cells than that in SW620 cells. The uptake of 18F-FLT closely correlated with the expression of HSP27 ( r =0.924,P =0.004) and Integrin β3 (r=0.813,P =0.025). 18F-FDG uptake inversely correlated with the survival of tumor-bearing mice (r =0.500,P=0.017). Conclusions The uptake of 18F-FDGand 18F-FLT may reflect different biological characteritics of CRC. High 18F-FLT uptake in CRC on PET scan may predict high metastatic tendency.