摘要
目的 探索脂质体介导的 99m Tc标记 c- myc m RNA反义寡核苷酸链的生物学特性。方法 合成15 bp的 c- myc m RNA的反义、正义和无义寡核苷酸链 ,用三氯乙酸沉淀测定脂质体包裹的 99m Tc标记的上述寡核苷酸链 (简称为 99m Tc- DNA)和未用脂质体包裹的 99m Tc- DNA的血浆蛋白结合率。用 BAL B/ c小鼠研究不同脂质体包裹的 99m Tc- DNA的生物学分布。用家兔研究脂质体介导的 99m Tc- DNA的药代动力学特性。结果 99m Tc- DNA的血浆蛋白结合率的范围为 34.81%～ 70 .5 3%。脂质体介导的 99m Tc- DNA的体内分布以网状内皮系统最高 ,胃、血和肠道其次 ,其余组织中放射性分布较少。其药代动力学曲线符合开放二室模型 ,t1 / 2α约为 2～ 5分钟 ,t1 / 2β约为 10 0～15 0分钟 ,血浆清除率小于 2 ml/ min。结论 99m Tc- DNA的血浆蛋白结合率高 ,脂质体介导的 99m Tc- DNA具有合适的生物半衰期 ,血浆清除快 。
Objective To probe the biological character of liposome mediated 99m technetium labeled antisense oligonucleotide of c myc mRNA, and lay the foundations for clinical research on antisense image or treatment. Methods Antisense, sense and scrambled oligonucleoyide, each containing 15 bases, were synthesized elsewhere. The rates of liposome entrapped 99m Tc DNA and 99m Tc DNA combination with plasma protein were tested through trichloroacetic acid precipitation. BALB/c mice were used to test the biodistribution in vivo, and rabbits were used to investigate the pharmacokinetics characters. Results Their rates of combination with plasma protein ranged from 34.81% to 70.53%. Reticuloendothelial system played an important role in the biodistribution; stomach, blood and intestines were less important; other tissues accumulated the least of the liposome mediated 99m Tc labeled c myc oligonucleotides. The pharmacokinetics of liposome entrapped 99m Tc DNA fitted the open dithecal model. Their distribution(t 1/2α ) half time was about 2 to 5 minutes, and clearance (t 1/2β ) half time about 100 to 150 minutes. Plasma clearance was smaller than 2ml/min. Conclusion The rate of 99m Tc DNA combination with plasma protein was high. The biological half time of liposome mediated 99m Tc DNA was proper. Plasma clearance was high. So liposome mediated 99m Tc DNA is a potential kind of radioactive agent.
出处
《华西医科大学学报》
CSCD
北大核心
2002年第1期15-18,22,共5页
Journal of West China University of Medical Sciences
基金
国家自然科学基金资助 (批准号 39870 2 0 0 )
