叶酸受体肿瘤显像剂99Tcm-（HYNIC—NHHN—FA）（EDDA）的制备及生物性能评价  

Preparation and biological evaluation of radiolabeled folate receptor.positive tumor agent 99TCm- （HYNIC-NHHN-FA） （EDDA）

作　　者：于倩[1] 谢芳[2] 杨文江[3] 陆洁[2] 梁志刚[1] 彭程[1] 

机构地区：[1]首都医科大学宣武医院核医学科,北京100053 [2]北京师范大学化学学院、放射性药物教育部重点实验室,100875 [3]中国科学院高能物理研究所核辐射与核能技术重点实验室,北京100049

出　　处：《中华核医学与分子影像杂志》2017年第1期15-19,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

摘　　要：目的制备99Tcm标记的FR靶向肿瘤分子探针99Tcm－（HYNIC－NHHN－FA） （EDDA），并评价其生物性能。 方法合成FA衍生物配体FA－NHHN－HYNIC，以EDDA作为共配体进行99Tcm标记，经HPLC纯化后，测定其放化纯、脂水分配系数和体外稳定性，选用FR高表达的人口腔表皮样癌KB细胞进行体外细胞结合实验，研究其在正常小鼠体内的生物分布及荷KB肿瘤裸鼠SPECT/CT显像。 结果标记配合物经HPLC纯化后放化纯大于95%，在生理盐水和小鼠血清中稳定性良好，可与FR高表达的KB细胞特异性结合，温育1 h后细胞总结合率可达（6.76±0.60）%，加入过量FA后摄取率降低至（0.24±0.02）%；正常小鼠体内生物分布显示其仅在FR高表达的肾脏有高放射性浓聚，给药后0.5 h肾脏摄取达（21.79±9.79） %ID/g。小动物SPECT/CT显像肿瘤部位清晰可见，且能被过量FA明显抑制。 结论标记物99Tcm－（HYNIC－NHHN－FA） （EDDA）是一种性能良好的FR靶向肿瘤分子探针。Objective To prepare a novel radiolabeled FR-positive tumor targeting agent 99Tcm- （HYNIC-NHHN-FA） （EDDA） and evaluate its biological properties. Methods FA derivative FA-NHHN- HYNIC was synthesized and radiolabeled with 99Tcm using EDDA as a coligand. The radiochemical purity, octanal/water partition coefficient and in vitro stabilities of the complex were studied after purified by HPLC. In vitro cellular uptakes were performed on FR-positive KB cells （human oral epidermoid carcinoma cells）. Biodistribution and microSPECT/CT imaging were investigated on normal Kunming mice and nude mice bearing KB tumors, respectively. Results The radiochemical purity of the complex was over 95% after pu- rified by HPLC. It displayed high stability both in saline and in serum. It also exhibited high specific FR binding in FR-positive KB cells in vitro. The binding ratio was （6.76±0.60）% 1 h after incubation, and de- creased to （0.24±0.02）% after adding excessive FA. The results of biodistribution showed high kidney uptake in normal mice, and the uptake reached （21.79±9.79） %ID/g 0.5 h after injection. Flank KB tumors were clearly visualized with 99Tern-（HYNIC-NHHN-FA） （EDDA） by microSPECT/CT imaging at 2 h postinjection, and the uptake could be inhibited by excessive FA. Conclusions 99TCm-（ HYNIC-NHHN- FA） （EDDA） exhibits good pharmacokinetic properties, suggesting its potential as a promising FA targeting agent for tumor imaging.

关 键 词：叶酸 同位素标记 锝 癌 体层摄影术 发射型计算机 单光子 体层摄影术 X线计算机 小鼠 

分 类 号：R730.44[医药卫生—肿瘤]