131I标记多肽YP13聚乙二醇修饰物及其生物分布

利用噬菌体展示技术, 对荷人结肠癌CL-187裸鼠进行体内筛选, 获得在肿瘤组织中富集的一条十二肽SVSVGMLPSHAP. 为了标记131I, 在N端连接酪氨酸合成了十三肽YP13(YSVSVGMLPSHAP). 另外, 利用单甲基化聚乙二醇(mPEG5000)对YP13进行化学修饰. RP-HPLC分离纯化YP13、mPEG-YP13和对照随机十三肽YR13(YEDIKPKTSLAFR) 131I标记产物, 放化纯度大于95%. RP-HPLC分析131I-YP13和131I-mPEG-YP13体内循环60 min后的血清, 结果显示, 131I-mPEG-YP13体内稳定性优于131I-YP13. 这三种标记物在荷人结肠癌CL-187裸鼠体内的分布表明, 131I-YP13和131I-mPEG-YP13在1和2 h时的肿瘤摄取远远高于对照肽131I-YR13, 二者的瘤血比随时间的延长而升高. 131I-mPEG-YP13在肿瘤中的摄取随着时间的延长有所改善. 因此, 放射性碘标记的多肽YP13及其聚乙二醇修饰物可能成为新型结肠癌显像剂.

Radioiodination and Biodistribution of PEGy Lated YP13 Polypeptide

A dodeca-peptide SVSVGMLPSHAP that targets human CL-187 tumor was identified in vivo by phage display technology. In order to evaluate the potency of YP13 as the imaging agent for diagnosis of tumor and to be easily radioiodinated, peptide YSVSVGMLPSHAP(YP13) with tyramine being added to the N-terminal was synthesized and chemically modified by conjugation with a low molecular weight monomethoxy polyethylene glycol(mPEG, Mw=5000). YP13, mPEG-YP13 and YR13(a nonspecific random 13 peptide as a control peptide) were labeled with 131I via Iodogen method. The labeled complex 131I-YP13, 131I-mPEG-YP13 and 131I-YR13 were isolated and purified by RP-HPLC. The radiochemical purity was estimated to be better than 95%. The RP-HPLC analysis of the supernatant of 131I-YP13 and 131I-mPEG-YP13 in serum collected for 60 min after injection shows that 131I-mPEG-YP13 in vivo was far more stable than 131I-YP13. The biodistribution of 131I-YP13, 131I-mPEG-YP13 and the control peptide 131I-YR13 in mice bearing human colon cancinoma was investigated. The experimental results indicate that there was higher uptake of 131I-YP13 and 131I-mPEG-YP13 in tumor than that of control peptide YR13 at 1 h and 2 h. The ratios of tumor to blood for 131I-mPEG-YP13 and 131I-YP13 increased as time prolonging. The longer serum half-life of mPEG-YP13 improved the uptake in tumor. Therefore, it can be expected that the radioiodinated YP13 and PEGylated YP13 may be a potential tumor-imaging agent.