新型放射性骨治疗剂^(117)Sn^m-TTHMP生物学性能的研究

Experimental study of the biological properties of^(117)Sn^m-TTHMP: a new potential radiophannaceutical for treating bone metastases

目的 探讨^(117)Sn^m-三乙撑四胺六甲撑膦酸(TTHMP)的生物学性能,以期开发新型放射性骨治疗剂。方法 以^(117)Sn^m-DTPA作对照,进行^(117)Sn^m-TTHMP新西兰兔平面骨显像和昆明种小白鼠体内分布实验。收集小鼠48 h尿液,计算^(117)Sn^m-TTHMP、^(117)Sn^m-DTPA在骨摄取高峰时相各重要脏器及全身放射性滞留量。结果 ①^(117)Sn^m-TTHMP兔骨显像提示骨摄取较高,颅骨、脊柱、四肢显示清晰,与^(117)Sn^m-DTPA骨显像效果相似。②^(117)Sn^m-TTHMP血液清除与骨摄取迅速,注射后1h骨摄取每克组织百分注射剂量率(％ID/g)为15.82,4 h为18.89,24h为25.23,14 d后仍高达15.39。肾脏为主要排泄器官,非靶脏器放射性残留低。③^(117)Sn^m-TTHMP骨摄取率高于^(117)Sn^m-DTPA,差异明显。结论 ^(117)Sn^m-TTHMP有良好的生物学性能,是一种新型极具发展潜力的放射性骨治疗剂,值得进一步研究。

Objective To investigate the biological properties of 117 Snm-triethylenetetraamine-hexa-meth-ylene phosphonic acid (TTHMP), a new kind of bone seeking compound and to explore a potential radiopharma-ceutical for target therapy of bone metastases. Methods With the contrast of117 Snm-DTPA, the plane bone scanning on New Zealand rabbits and the biodistribution experiments on Kunming mice were performed. Results ① The plane bone scanning of rabbits showed that117Snm-TTHMP was principally absorbed by skeletal system. The skull, spine and legs can be observed clearly, which was similar with the images of117 Snm-DTPA in clarity. ② Mice experiments showed the high bone seeking of117Snm-TrHMP. The skeletal uptakes were 15.82 ,18.89 and 25.23 %ID/g, respectively at 1, 4, 24 h after the injection and kept on 15.39% ID/g 14 d later. Kidney seemed to be the major excretory organ of it. The blood clearance was quick and the retention in non-target organs was low. ③The percentage of bone uptake of117 Snm-TTHMP was higher than that of117 Snm-DTPA, and the statistical difference was significant. Conclusion 117 Snm-TTHMP shows fine biological properties which can be compared favorably with the commonly used bone radioactive agent, and it is well worth further research as a promising potential radiopharmaceutical in nuclidic treatment for bone metastases.