^(131)Ⅰ标记NGR聚乙二醇修饰物及其生物分布  

Radioiodination and Biodistribution of PEGylated NGR Peptides

作　　者：杨顺龙[1] 褚泰伟[1] 刘新起[1] 王祥云[1] 

机构地区：[1]北京大学化学与分子工程学院应用化学系,北京100871

出　　处：《核化学与放射化学》2005年第2期75-81,共7页Journal of Nuclear and Radiochemistry

基　　金：国家自然科学基金资助项目(20301001)

摘　　要：天门冬酰胺酰甘氨酰精氨酸(NGR)是特异性地定位于肿瘤新生血管受体的多肽基序,在肿瘤诊断和治疗方面具有潜在的应用前景。首先用两种单甲基化聚乙二醇(mPEG1900,mPEG5000)对YGGCNGRC环肽进行化学修饰,并进行131Ⅰ标记。考察了这些标记物在正常小鼠以及荷乳腺癌MCF7裸鼠体内的分布。结果表明,131ⅠmPEG1900YGGCNGRC和131ⅠmPEG5000YGGCNGRC在各个器官和组织中的摄取率与131ⅠYGGCNGRC相比都有所降低,但在肾脏中的摄取率增高。血液初始摄取稍有下降,从血液中清除的速率则无显著差别。用mPEG5000修饰的NGR环肽显著地降低了131Ⅰ的脱落。虽然131ⅠmPEG5000YGGCNGRC在肿瘤中的摄取比131ⅠYGGCNGRC稍低,但肿瘤组织与正常组织的摄取比对多数器官和组织都有所提高,其中肿瘤与肌肉的摄取比由3.5±1.7提高到5.7±2.2。修饰与否对肿瘤与血的摄取比影响不大,由0.73±0.33变化至0.80±0.22。The NGR peptide is a ligand specifically binding to tumor angiogenic blood vessels, and thus has potential usage in the diagnosis and therapy of tumor. In this study, the cyclic peptide YGGCNGRC is chemically modified by conjugation with a low molecular weight monomethoxy polyethylene glycol (mPEG, M. W. 1 900 or 5 000). They are labeled with 131 I by using the Iodogen method . The biodistribution results in normal mice and mude mice bearing MCF-7 breast carcinoma show that ~ 131 I-PEG 1900 -YGGCNGRC and 131 IPEG 5000 -YGGCNGRC have lower uptake in most organs and tissues, but higher renal uptake than ~ 131 I-YGGCNGRC . Their early uptake in blood is lowered and their retention kept approximately the same as ~ 131 I-YGGCNGRC . The deiodination from ~ 131 I-PEG_ 5000 -YGGCNGRC is significantly lower than from ~ 131 I-YGGCNGRC . Although the tumor uptake of ~ 131 I-PEG 5000- YGGCNGRC is a little bit less than ~131 I-YGGCNGRC , the uptake ratio of tumor to normal tissue is increased for most examined organs. The tumor/muscle ratio is increased from 3.5±1.7 to 5.7±2.2. Modification of cyclic NGR peptide with mPEG does not remarkably alter the tumor/blood ratio.

关 键 词：肿瘤新生血管 NGR多肽 聚乙二醇 ^131Ⅰ标记 生物分布 

分 类 号：O615.42[理学—无机化学]