Abstract: 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.

Key words: Hypoxia, HL91, Endostatin gene, ³²P