血管抑素的^(131)I标记及其对裸鼠A549肺肿瘤的作用

Labeling of Angiostatin With ^(131)I and Its Antitumor Effect on Nude Mice With A549 Cells

采用一步法从人血浆中分离血管抑素(Angiostatin,AS),并用L-Lysine Sepharose 4B作亲和层析纯化;将提纯的AS用Iodogen固相法进行131I标记,分析131I-AS的标记率、比活度,并评价其体外稳定性;32只荷A549肺肿瘤的裸鼠随机分为4组,腹腔注射131I-AS(含11.1 MBq131I,AS为12.5 mg/kg)1、31I 11.1MBq、AS 12.5 mg/kg和生理盐水0.3 mL,1次/周,治疗4周,观察28 d内肿瘤体积的变化。结果显示,131I-AS标记率为77.8%~86.7%,比活度为1.28~3.96 TBq/g,放化纯度为98.6±0.26%。标记产物-20℃存放7 d,放化纯度降至72%;治疗28 d后,131I-AS组1、31I组、AS组和生理盐水组小鼠肿瘤的体积分别是(1 956±98)(、5 284±123)(、3 948±115)(、7 350±153)mm3。以上结果提示,131I-AS能较强地抑制小鼠体内移植肿瘤的生长,其抑制作用优于单纯应用等浓度的AS及131I,131I-AS在治疗肿瘤中有潜在的应用前景。

The angiostatin （AS） which is separated from human plasma and purified are labeled with ^131I using Iodogen method. 32 male nude mice with A549 ceils are divided into four groups and injected with ^131I-AS （^131I 11.1 MBq , AS 12.5 mg/kg）, ^131I（11. 1 MBq）, AS（12.5 mg/kg）, normal saline （0.3） mL. Each drug is given intraperitoneally and injected for four times at an interval of 7 days respectively . The volume of tumors is measured during 28 days after treatment. The labeling efficiency is 77.8%-86.7% , the specific activity is 1.28-3.96 TBq/g. The radiochemical purity of ^131I -angiostatin reduced to 72 % after 7 days in vitro storage （-20 ℃）. The mean volume of transplanted tumors in the mice with A549 lung carcinoma is （1 956±98）,（5 284±123）.（3 948±115）.（7 350±153）mma after treated with ^131I -angiostatin, ^131I ,angiostatin and NS respectively. Compared with the NS group, the tumor inhibition rate in the other 3 groups are 70.95%,25.05% and 54.55% .The results suggest that ^131I -angiostatin has potential prospect of clinical application in the treatment of solid tumor.