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

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

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4 h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2 h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2 h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，1 h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。

Objective To synthesize ^99Tc^m-（HYNIC-BMS-200261）（tricine）（trisodium triphenylphosphine-3, 3＇, 3″-trisulfonate）（^99Tc^m-（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 ^99Tc^m-labeling. The radiochemical purity and stability of ^99Tc^m-（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 ^99Tc^m-（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. ^99Tc^m-（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 ^99Tc^m-（HYNIC-BMS-200261）（tricine） （TPPTS） may be easily prepared with high radiochemical purity and stability. The imaging results and biodistribution characteristics suggest it may be promising for the detection of breast cancer.