利用乏氧显像评估针对乳腺癌血管的治疗

目的 应用内皮抑素基因和³²P-磷酸铬胶体内照射治疗大鼠乳腺癌种植瘤,并利用乏氧显像剂^99mTc-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(^99mTc-HL91)评估治疗后肿瘤乏氧状况的变化。方法 80只雄性Wistar大鼠皮下注射Walker-256乳腺癌细胞,通过瘤内注射的方式给药,建立种植瘤模型并随机分为四组:对照组(0.9%生理盐水)、³²P组(³²P-磷酸铬胶体)、endo组(含endostatin基因的质粒)和³²P+endo组(³²P-磷酸铬胶体和含endostatin基因的质粒的混合物),治疗起始和治疗后7天,进行^99mTc-HL91乏氧显像,计算各组大鼠肿瘤部位与对侧正常组织放射性计数比值(T/NT)。每4天测量肿瘤大小,计算肿瘤生长率,治疗20天后取肿瘤组织染色,计算各组大鼠肿瘤微血管密度(MVD)、凋亡指数(AI)、血管内皮生长因子(VEGF)的阳性率。结果 ³²P组和endo组肿瘤生长率低于对照组,³²P+endo组最低(P＜0.001)。³²P组MVD、VEGF高于对照组(P＜0.05),endo组和³²P+endo组低于对照组(P＜0.05)。³²P组和endo组AI高于对照组,³²P+endo组最高(P＜0.001)。endo组和³²P+endo组T/NT比值高于对照组和³²P组(P＜0.05)。结论 肿瘤经不同治疗方法后乏氧的改变各不相同,^99mTc-HL91能在体内监测肿瘤的乏氧状况,从而早期评估肿瘤血管抑制剂的治疗效果。

Application of hypoxia imaging to assess vascular therapies for breast cancer

Objective The Objective of this study was to use endostatin gene and ³²P-chromic phosphate colloid to treat implanted tumor of breast cancer in rats,and the hypoxic imaging agent ^99mTc-4,9-diazepine-3,3,10,10-tetramethyldodecane-2,11-diketoxime(^99mTc-HL91)was used to evaluate the changes of tumor hypoxia after treatment. Methods Eighty male Wistar rats were subcutaneously injected with walker-256 breast cancer cell to establish implanted tumor models and randomly divided into 4 groups,which were administered by intratumoral injection:the control group(0.9% normal saline),³²P group(³²P-chromium phosphate colloid),endostatin(endo)group(plasmid containing endostatin gene)and ³²P+endo group(mixture of ³²P-chromium phosphate colloid and plasmid containing endostatin gene).^99mTc-HL91 hypoxia imaging was performed at the beginning of treatment and 7 days after treatment,and the ratio of radioactive count(T/NT)between the tumor site and contralateral normal tissue of rats in each group was calculated.The tumor size was measured every 4 days,and the tumor growth rate was calculated.After 20 days of treatment,the tumor tissues were stained,and the positive rates of tumor microvessel density(MVD),apoptosis index(AI)and vascular endothelial growth factor(VEGF)in rats in each group were calculated. Results The tumor growth rate in the ³²P group and endo group was lower than that in the control group,and the tumor growth rate in the ³²P+endo group was the lowest(P＜0.001).MVD and VEGF in the ³²P group were higher than those in the control group(P＜0.05),and those in the endo group and ³²P+endo group were lower than those in the control group(P＜0.05).The AI in the ³²P group and endo group was higher than that in the control group,and the AI in the ³²P+endo group was the highest(P＜0.001).The ratio of T/NT in the endo group and ³²P+endo group was higher than that in the control group and ³²P group(P＜0.05). Conclusion The changes of hypoxia in tumors after different treatment methods are different.^99mTc-HL91 can monitor the hypoxic status of tumors in vivo,so as to evaluate the therapeutic effect of tumor blood vessel inhibitors in the early stage.