^(99m)Tc标记丝状噬菌体肽库及其在正常小鼠体内的分布(英文)  

Radiolabeling of Filamentous Phage Peptide Library With ^(99m)Tc and Its Biodistribution in Normal Mice

作　　者：孙丽艳[1] 褚泰伟[1] 王祥云[1] 

机构地区：[1]北京分子科学国家实验室北京大学化学与分子工程学院应用化学系,北京100871

出　　处：《生物化学与生物物理进展》2006年第12期1200-1206,共7页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(20301001);国家重点基础研究发展计划(2006CB705700)资助项目~~

摘　　要：利用噬菌体展示技术已选出了多条与靶结合的肽.然而,即使是体内直接筛选得到的,肽与肿瘤或靶器官的体内结合并不理想.为了更好地理解噬菌体在体内的循环,通过MAG399mTc标记噬菌体肽库,研究了肽库在体内分布.体内分布实验结果显示,99mTc-噬菌体主要分布在肝和脾中,而心脏、肌肉、脑和胰腺这些器官或组织中的分布非常低.99mTc-噬菌体在胃、肠和骨中的累积,随着时间延长在不断升高,其他器官中的吸收则在不断降低.从5min到30min,99mTc-噬菌体在血中清除迅速.当噬菌体在体内循环足够长的时间后,一些噬菌体颗粒可以穿透血管进入并内化在器官或组织中.总之,为了筛选具有高特异性和亲和性的肽,应该根据靶器官和筛选部位的不同,在筛选前确定合适的噬菌体在体内的循环时间.Numerous peptides that bind to a given target have been selected by phage display technology. However, some peptides isolated to date do not bind with high affinity to tumor or organ sites, even peptides were selected in vivo. Therefore, the biodistribution of ^99mTc-labeled filamentous phage peptide library via MAG3 （mercaptoacetyltriglycine） were investigated to gain a better understanding of phage circulation in vivo. The experimental results showed that the liver and spleen were the organs of the greatest accumulation, while heart, muscle, pancreas and brain retained less radioactivity. In opposite to other tissues and organs, the radioactivity in stomach, intestine and bone gradually went up with time. The clearance of ^99mTc-labeled phage in blood was very fast from 5 min to 30 min and then slowed down. When phage in vivo circulated at enough long period of time, some phage particles could extravasate in some organs or tissues and internalized there. In conclusion, the circulation time of phage in vivo should be experimentally determined beforehand according to the targeted organs and the specific location of target peptides in order to panning a peptide with high specificity and affinity to that target.

关 键 词：丝状噬菌体肽库 生物分布 标记 ^99MTC 

分 类 号：O615.42[理学—无机化学] Q785[理学—化学]