Synthesis and in vivo evaluation of Tc-99m-labeled cyclic CisoDGRC peptide conjugates for targeting αvβ3 integrin expression.
Synthesis and in vivo evaluation of Tc-99m-labeled cyclic CisoDGRC peptide conjugates for targeting αvβ3 integrin expression.
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用于靶向 αvβ3 整合素表达的 Tc-99m 标记的环状 CisoDGRC 肽缀合物的合成和体内评估。
DOI：
10.1016/j.bmcl.2010.08.082
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发表时间：
2010
影响因子：
2.7
通讯作者：
Gali,Hariprasad
中科院分区：
文献类型：
--
作者：
Pathuri,Gopal;Sahoo,Kaustuv;Awasthi,Vibhudutta;Gali,Hariprasad
合成了两个αvβ3整合素结合肽偶联物，包含环状CisoDGRC基序、一个连接剂和一个螯合剂，使Tc-99m能够通过face -[99mTc(CO)3]+核心进行标记。注射后1小时U87MG荷瘤裸鼠体内生物分布研究显示，该连接体对血流中放射性示踪剂的清除有深远的影响。在体内阻断研究表明，选择性结合肿瘤表达αvβ3-整合素和其他组织。尸体解剖收集的尿液样本的HPLC分析显示没有降解，表明其代谢稳定性。这些结果表明，环状CisoDGRC基序可以作为αvβ3靶向载体，通过适当选择肽与有效载荷之间的连接物来获得最佳的药动学特性。
Two αvβ3integrin-binding peptide conjugates containing the cyclic CisoDGRC motif, a linker, and a chelator to enable Tc-99m labeling via the fac-[99mTc(CO)3]+core were synthesized. In vivo biodistribution studies in U87MG tumor-bear nude mice at 1h post-injection revealed a profound effect of the linker on the clearance of the radiotracer from the blood stream. In vivo blocking studies demonstrated the selective binding to the tumors expressing αvβ3-integrin and other tissues. The HPLC analysis of urine samples collected upon necropsy showed no degradation indicating their metabolic stability. These results suggest that cyclic CisoDGRC motif could be exploited as a new αvβ3-targeting vector by an appropriate selection of a linker between the peptide and the payload to obtain optimum pharmacokinetic properties.