153Sm-EDTMP-纳米羟基磷灰石的生物学性能

目的研究^153Sm-乙二胺四甲撑膦酸(EDTMP)-纳米羟基磷灰石(HA)的体内外生物学性能。方法采用溶胶-凝胶法合成纳米HA并用电镜和X线衍射进行鉴定，采用独立变数法研究^153Sm-EDTMP-纳米HA的最佳标记条件并对产物进行体外稳定性分析，进行^153Sm-EDTMP-纳米HA新西兰兔显像，比较纳米HA、^153Sm-EDTMP和^153Sm-EDTMP-纳米HA对肝癌SMMC-7721和乳腺癌MCF-7细胞的体外抑制作用。结果①纳米HA为针状结晶，结晶度较好，径向10～30nm，轴向70～100nm，X线衍射证明产物为HA。②^153Sm-EDTMP-纳米HA的标记率均在95％以上。体外稳定性好，在生理盐水中放置48h后放化纯仍大于95％。③正常新西兰兔^153Sm-EDTMP-纳米HA显像对比度较好，骨骼系统显示清晰，肾脏显影，血清中放射性下降较快。④^153Sm-EDTMP-纳米HA对肝癌SMMC-7721和乳腺癌MCF-7细胞的半抑制率质量浓度分别为1．98mg／L和0．075mg／L，而纳米HA分别为3．31mg／L和0．52mg／L，^153Sm-EDTMP分别为4．32mg／L和0．67mg／L，^153Sm-EDTMP-纳米HA对肿瘤生长的抑制率明显高于纳米HA和^153Sm-EDTMP。结论^153Sm-EDTMP-纳米HA的骨组织摄取好，有明显的体外抑制肿瘤生长的作用。

Experimental study of the biological properties of 153Sm-nano-Hydroxyapatite

Objective To investigate a new agent 153 Sm ethylene diamine tetramethylene phosphonic acid (EDTMP) nano Hydroxyapatite(nano HA) and the in vitro and in vivo performance of three derivatives of this agent aiming to explore a new radiopharmaceutical for targeting therapy of bone metastases. Methods The nano HA was synthesized by collosol gelatum method, and was evaluated by transmission electron microscope (TEM) and X ray diffraction (XRD). 153 Sm was produced with a high specific activity and excellent radionuclidic purity; adopting independent variable method, that nano HA being labeled with 153 Sm by EDTMP transfer ligands in the best condition was investigated. The stability of 153 Sm EDTMP nano HA in vitro was studied. 153 Sm EDTMP nano HA was injected into normal rabbits for in vivo study. Both SMMC 7721 and MCF 7 cell lines were divided into three groups, treated with nano HA, 153 Sm EDTMP and 153 Sm EDTMP nano HA, respectively, and the survival rate was measured by mono nuclear cell direct cytotoxicity assay method. Results The detection with TEM, XRD showed that nano HA consisted of needle like microcrystals. The labelling rate of 153 Sm EDTMP nano HA was more than 95%, and was extremely stable in vitro. The scanning of normal rabbits showed that the skeletal system was clear, but other systems, for example, liver, spleen and kidney also were seen. The cell culture experiments in vitro indicated that 153 Sm EDTMP nano HA strongly inhibited the proliferation of SMMC 7721 and MCF 7 cells. The half effective inhibition concentrations of 153 Sm EDTMP nano HA were 1.98 and 0.075 mg/L, respectively; the half effective inhibition concentrations of nano HA were 3.31 and 0.52 mg/L, respectively; the half effective inhibition concentrations of 153 Sm EDTMP were 4.32 and 0.67 mg/L, respectively. Conclusion 153 Sm EDTMP nano HA shows it's fine biological properties, and it is well worth further researching as a promising radiopharmaceutical in nuclidic treatment for bone metastases.