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99Tcm-(HYNIC-BMS-200261)(tricine)-(TPPTS)的制备及对荷乳腺癌裸鼠的显像研究

Preparation of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) and its biodistribution and preliminary imaging study in nude mice bearing human breast cancer

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目的 制备99Tcm-(HYNIC-BMS-200261)(N-三羟甲基甘氨酸)(三苯基膦三间磺酸钠盐)[99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS)]三重配位化合物,评价其在正常小鼠及荷乳腺癌裸鼠体内的生物分布,并对荷乳腺癌裸鼠进行初步显像研究.方法 先用双功能螯合剂HYNIC与BMS-200261耦联,再以tricine和TPPTS为协同配体,进行99Tcm标记,合成三重配位化合物99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS),测定其放化纯及稳定性,并进行正常小鼠、荷乳腺癌MDA-MB-435裸鼠体内生物分布实验和荷乳腺癌裸鼠γ显像.结果 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS)的放化纯>90%,室温下放置4h其放化纯仍大于85%.正常小鼠体内分布结果表明,该标记物的血液清除迅速,注射后2h血液中的放射性摄取值为(0.08±0.02) %ID/g,主要经肝、肾排泄,脾、胃肠道摄取较少,注射后2h脾、胃、小肠中的放射性摄取值分别为(0.35±0.13)、(0.27±0.11)和(0.25±0.07) %ID/g.荷乳腺癌MDA-MB-435裸鼠在注药后30 min显像即可见肿瘤部位有放射性浓聚影,1h后T/NT比值最高,达3.40±0.30.结论 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS)三重配位化合物制备成功,标记方法可行,放化纯高,稳定性好,生物分布特性良好,有望用于乳腺癌显像研究.

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Objective To synthesize 99Tcm-(HYNIC-BMS-200261) (tricine) (trisodium triphenylphosphine-3,3',3"-trisulfonate) (99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS)) and evaluate its biodistribution and feasibility of imaging in nude mice bearing human breast cancer xenografts.Methods HYNIC was conjugated to BMS-200261,then tricine and TPPTS were used as coligands for 99Tcm-labeling.The radiochemical purity and stability of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) were measured with HPLC.Biodistribution in normal mice and imaging in nude mice bearing MDA-MB-435 breast cancer xenografts were performed respectively.Results The radiochemical purity of 99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS) was over 90%,and remained over 85% after 4 h at room temperature.The biodistribution data in normal mice showed a rapid clearance from blood.The tracer uptake of blood was (0.08±0.02) %ID/g at 2 h postinjection.99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS) was excreted mainly via the liver and kidneys.There was little radioactivity accumulation in gastrointestinal tract.The tracer uptake of spleen,stomach and small intestine were (0.35±0.13),(0.27±0.11) and (0.25±0.07) %ID/g at 2 h postinjection.Gamma imaging showed the tumor tissue uptake was remarkable at 30 min postinjection,with the maximum T/NT ratio of 3.40±0.30 at 1 h postinjection.Conclusions 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) may be easily prepared with high radiochemical purity and stability.The imaging results and biodistribution characteristics sug,gest it may be promising for the detection of breast cancer.

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