肺癌特异性靶向多肽的^(131)I标记及其对小鼠的急性毒性试验

Radiolabeling of Polypeptide for Specific Targeting Lung Cancer and Its Acute Toxicity in Normal Mice

目的:探讨肺癌特异性靶向小分子多肽的131I标记方法,观察131I标记多肽及未修饰多肽静脉注射小鼠后的急性毒性试验。方法:小分子多肽的氨基酸序列为cNGQGEQc,在固相合成多肽的过程中直接完成多肽与酪氨酸的偶联,然后采用氯胺-T法进行多肽的131I标记。取72只小鼠,分为3组,每组24只小鼠,第一组和第二组分别为经腹腔注入50μg/0.7ml未修饰多肽cNGQGEQc和18.5MBq/0.7ml标记多肽131I-cNGQGEQc溶液,第三组为经腹腔注射0.7ml生理盐水。给药后分别观察各组小鼠的急性毒性反应。结果:与生理盐水对照组相比较,腹腔注入未修饰多肽cNGQGEQc组和131I-cNGQGEQc多肽组小鼠全部成活,一般状态正常,体重增长,未见明显急性毒副反应。结论:未修饰多肽及131I标记多肽经腹腔途径给药后,在小鼠体内没有引起明显的急性毒副反应。

Objective To establish a radiolabeling method of specific polypeptide for lung cancer targeting with 131I and report the acute toxicity in normal mice of injections of iodine labeled and unlabelled polypeptide.Methods Amino acid sequence of polypeptide was cNGQGEQc.The tyrosine was directly conjugated with peptide cNGQGEQc during its synthesis.Radiolabeling of polypeptide with 131I was performed by chloramine-T method.72 normal mice were randomly divided into three groups,each group had 24 mice.The first and second groups received,intraperitoneal injection of unlabelled polypeptide with 50μg/0.7ml and 131I labeledpolypeptide with 18.5MBq/0.7ml respectively,and the third group was intraperitoneally injected with 0.7ml normal saline.The acute toxicity reaction was observed in mice of each group after injection.Results Compared to control group of normal saline,there were no obvious acute toxicity in the group with unlabelled polypeptide and the group with 131I-cNGQGEQc in which all the mice were alive with normal physical conditions and body weight increasing.Conclusion No apparent acute toxic reaction was observed in mice received with unlabelled polypeptide and 131I-cNGQGEQc polypeptide.