CAJ | 학술논문

目的探讨以动态增强磁共振(DCE-MRI)参数评价抗血管生成药物靶向治疗肿瘤早期效果的可行性及价值.方法将人结肠癌HT-29细胞悬液接种于20只BALB/C-nu裸鼠右后肢皮下.将裸鼠均分为实验组和对照组,每组均为10只,实验组腹腔注射贝伐单克隆抗体,对照组注射等量的0.9％氯化钠溶液.分别于给药前和给药后1、24、48 h对实验动物行DCE-MRI扫描,分析传输常数、回流常量、血管外细胞外容积分数(Ve)和增强曲线下初始面积(iAUC).给药48 h后处死实验动物,利用免疫组织化学方法检测瘤体微血管密度(MVD).DCE-MRI参数行方差分析.DCE-MRI参数与MVD间行Pearson相关性分析.结果在DCE-MRI成像中,裸鼠皮下结肠癌移植瘤瘤体边缘区域呈明显渐进性强化,伪彩图显示高灌注,中心区域强化程度较低,为低灌注.实验组不同时间点回流常量差异有统计学意义(F=3.752,P=0.016),其他DCE-MRI参数均差异无统计学意义(P均＞0.05).给药前和给药后1h,传输常数和回流常量两组间比较差异均无统计学意义(P均＞0.05).治疗后24 h和48 h,同时间点传输常数和回流常量实验组[24 h时分别为(0.095±0.039) min-1和(0.297±0.141) min-1,48 h时分别为(0.090±0.033) min-1和(0.314±0.148) min-1]与对照组[24 h时分别为(0.150±0.074) min-1和(0.494±0.126) min-1,48 h时分别为(0.171±0.045) min-1和(0.441±0.092) min-1]间比较差异均有统计学意义(F24h=4.824和11.386,F48h=22.605和5.455,P均＜0.05).各时间点iAUC和Ve两组间比较差异均无统计学意义(P均＞0.05).实验组血管内皮较对照组稀疏.传输常数、回流常量均与MVD正相关(r=0.745和0.400,P均＜0.05).结论 DCE-MRI参数传输常数和回流常量或可用于监测抗肿瘤血管生成药物靶向治疗结肠癌的早期效果.
목적 탐토이동태증강자공진(DCE-MRI)삼수평개항혈관생성약물파향치료종류조기효과적가행성급개치.방법 장인결장암HT-29세포현액접충우20지BALB/C-nu라서우후지피하.장라서균분위실험조화대조조,매조균위10지,실험조복강주사패벌단극륭항체,대조조주사등량적0.9％록화납용액.분별우급약전화급약후1、24、48 h대실험동물행DCE-MRI소묘,분석전수상수、회류상량、혈관외세포외용적분수(Ve)화증강곡선하초시면적(iAUC).급약48 h후처사실험동물,이용면역조직화학방법검측류체미혈관밀도(MVD).DCE-MRI삼수행방차분석.DCE-MRI삼수여MVD간행Pearson상관성분석.결과 재DCE-MRI성상중,라서피하결장암이식류류체변연구역정명현점진성강화,위채도현시고관주,중심구역강화정도교저,위저관주.실험조불동시간점회류상량차이유통계학의의(F=3.752,P=0.016),기타DCE-MRI삼수균차이무통계학의의(P균＞0.05).급약전화급약후1h,전수상수화회류상량량조간비교차이균무통계학의의(P균＞0.05).치료후24 h화48 h,동시간점전수상수화회류상량실험조[24 h시분별위(0.095±0.039) min-1화(0.297±0.141) min-1,48 h시분별위(0.090±0.033) min-1화(0.314±0.148) min-1]여대조조[24 h시분별위(0.150±0.074) min-1화(0.494±0.126) min-1,48 h시분별위(0.171±0.045) min-1화(0.441±0.092) min-1]간비교차이균유통계학의의(F24h=4.824화11.386,F48h=22.605화5.455,P균＜0.05).각시간점iAUC화Ve량조간비교차이균무통계학의의(P균＞0.05).실험조혈관내피교대조조희소.전수상수、회류상량균여MVD정상관(r=0.745화0.400,P균＜0.05).결론 DCE-MRI삼수전수상수화회류상량혹가용우감측항종류혈관생성약물파향치료결장암적조기효과.
Objective To explore the feasibility and value of dynamic contrast-enhanced (DCE-MRI) parameters in assessing early effects of anti-angiogenesis medicine in targeted therapy for tumors.Methods Twenty BALB/C-nu nude mice were injected subcutaneously with human colon cancer cells HT-29 to the right hind leg.The nude mice were evenly divided into the experimental group and control group with 10 mice in each group.The mice of experimental group were intraperitoneally injected with bevacizumab,and the control group were injected with the same volume of saline.DCE-MRI was performed before medication and one hour,24 h and 48 h after medication.The Ktrans,Kep,Ve and initial area under enhancement curve (iAUC) of DCE-MRI were analyzed.The animals were sacrificed 48 hours after medication.Microvessel density (MVD) of the tumors was detected by immunohistochemistry.One way analysis of variance was performed to analyze parameters of DCE-MRI.The Pearson correlation coefficient was used to analyze the correlation between parameters of DCE-MRI and MVD.Results Under DCE-MRI,the edge of subcutaneous colon cancer xenografts was obviously gradually enhanced,pseudo color indicated high perfusion,the strength degree of the central region was low and which meant low perfusion.The differences in Kep of different time point of experimental group were statistically significant (F=3.752,P=0.016) ; there as no significant difference in other parameters of DCE MRI (all P＞0.05).There was no significant difference in Ktrans and Kep before medication and one hour after medication (all P＞0.05).There were significant difference in Ktrans and Kep 24 hour and 48 hour after medication between experimental group (24 hour∶ (0.095 ± 0.039) min-1 and (0.297 ± 0.141) min-1,48 hour∶ (0.090±0.033) min 1 and (0.314±0.148) min-1) and control group (24 hour∶ (0.150±0.074) nin-1 and (0.494±0.126) min-1,48 hour∶ (0.171±0.045) min-1 and (0.441± 0.092) min-1) (F24h =4.824 and 11.386,F48h =22.605 and 5.455,all P＜0.05).There was no significant difference in Ve and iAUC between two groups at different time points (all P＜0.05).MVD of experimental group was lower than that of control group.Ktrans and Kep were positively correlated with MVD (r=0.745 and 0.400,both P＜0.05).Conclusion Ktrans and Kep parameters of DCE-MRI may be used in monitoring the earlier effects of anti-angiogenesis medicine in targeted therapy for colon cancer.