99Tcm直接法标记Angiostatin及其在荷瘤小鼠体内研究

目的:99Tcm直接法标记血管抑素(angiostatin,AS),观察其在荷瘤小鼠体内的生物分布并进行显像,以探讨其在监测肿瘤对抗血管生成治疗的应答中的价值. 方法:氯化亚锡还原法进行AS的99Tcm标记,纸层析法测标记率;用人脐静脉内皮细胞系(ECV304)观察其生物活性;为了明确99Tcm-AS与肿瘤的结合,是否存在受体特异性,我们进行了封闭实验. 在给药前2 h用未标记AS预处理荷乳腺癌EMT6瘤株的BALB/c小鼠,尾静脉注射99Tcm-AS,观察其体内分布并进行显像. 结果:氯化亚锡还原法标记AS可获得较高的标记率(>95%),其抑制内皮细胞生长的生物活性与AS相似. 在荷瘤小鼠体内分布结果显示:肿瘤的摄取率随着时间延长而增加,在注射99Tcm-AS后2～12 h,肿瘤可清晰显像,同时,用未标记AS预先封闭肿瘤可使肿瘤对99Tcm-AS摄取率下降. 结论:99Tcm-AS在荷瘤小鼠体内可浓聚于肿瘤,肿瘤对显像剂的摄取存在一定的特异性;99Tcm-AS有可能在肿瘤抗血管生成治疗疗效评价中发挥作用.

Direct labeling of angiostatin with 99Tcm and its distribution in tumor bearing mice

AIM: To observe the distribution of direct labelled angiostatin (AS) by 99 Tc m in tumor bearing mice and to evaluate the value of 99 Tc m AS in positive imaging of tumor. METHODS: Angiostatin was labeled by stannous reduced approach and the labeling efficiency was examined by TLC. The bioactivity of 99 Tc m AS was observed using human umbilical vein epithelial cell line (CEV304). Blocking experiment was conducted to make sure that the combination of tumor and 99 Tc m AS was related to angiostatin receptors. The EMT6 tumor bearing BALB/c mice were pretreated with non labeled angiostatin 2 h before administration of 99 Tc m AS. 99 Tc m AS was injected via tail vein, the distribution of 99 Tc m AS in vivo was observed and imaging was made. RESULTS: The labeling efficiency (>95%) of 99 Tc m AS was high and its bioactivity was the same as that of non labeled AS. Its distribution in tumor bearing mice indicated that the uptake of 99 Tc m AS increased gradually 2-12 h after 99 Tc m AS injection and the positive image of tumor was displayed clearly. The blocking with non labeled AS decreased the uptake of 99 Tc m AS. CONCLUSION: 99 Tc m AS can gather in tumors in mice and this specific binding may be related to the receptors of AS. 99 Tc m AS probably can be used in predicting the effects of anti angiogenesis therapy in tumor treatment.