摘要
目的探讨超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)标记的c-erbB2反义寡脱氧核苷酸探针在新西兰大白兔及BALB/c小鼠体内的药动学及主要脏器分布。方法 18只新西兰大白兔随机分为高、中、低剂量3组,选择注射前30 min、注射后1、3、5、10、20、40、60、120、180、360、720 min等时间点,从对侧耳缘静脉采血,测定铁含量以了解探针的药动学;BALB/c小鼠60只随机分为MR扫描组及取脏器组,在注射反义探针后10、30、60、180、360 min这5个时间点,同步进行MR扫描及取肝、脾、心、肾、肌肉标本,测定观察脏器的信噪比及铁含量,观察反义探针在BALB/c小鼠的主要脏器分布。结果高、中、低剂量的反义探针注射后的药动学符合二室模型,半衰期长;反义探针在脾脏富集量最高,以下依次为肝脏、肌肉、心脏及肾脏。结论了解反义探针在活体内的药动学及主要脏器分布,可以为进一步的活体MR成像时间及剂量选择等提供依据。
OBJECTIVE To investigate the pharmacokinetic parameters and main organ distribution of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticlcs in new Zealand white rabbits and BALB/c mice. METHODS Eighteen new Zealand white rabbits randomly divided into high, middle and small dose groups. Blood was taken to measure iron content from offside ear edge vein 30 min before and 1,3, 5, 10, 20, 40, 60, 120, 180,360 and 720 min after injection. The pharmacokinetic parameters were calculated. 60 BALB/c mice were randomly divided into MR scan and organ extract groups. Synchronous MR scan and ertout of liver, spleen, heart, kidney and muscle were carried out 10, 30, 60, 180 and 360 min after injection, the signal-noise ratio and organ iron content were measured to find out the organ distribution. RESULTS The pharmacokinetics of high, middle and small dose anfisense probe complied with two-compartment model with long half-life. The highest concentration was found in spleen; followed by liver, muscle, heart and kidney. CONCLUSION This study has found out the pharmacokinetic parameters and main organ distribution of antisense probe, which provides basis for the time and dose of in vivo MR imaging.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2011年第21期1656-1660,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金(30940021
30070230)
重庆市自然科学基金(2008BB5209)
重庆市卫生局医学科研基金(062025)
重庆医科大学优秀博士基金(2006-182)
重庆医科大学附属第一医院科研基金(YXJJ2009-08)
关键词
反义寡脱氧核苷酸
超顺磁性氧化铁
药动学
antisense oligodeoxynucleotide
superparamagnetic iron oxide
pharmacokinetics
