A new 18F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging.
A new 18F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging.
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DOI：
10.1007/s00726-010-0762-5
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发表时间：
2011-07
期刊：
影响因子：
3.5
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Yan, Yongjun;Chen, Kai;Yang, Min;Sun, Xilin;Liu, Shuanglong;Chen, Xiaoyuan
肽异二聚体包含两种不同的受体靶向肽配体。与母体单受体靶向肽单体相比，基于双受体靶向肽异二聚体的分子成像探针对多受体表达肿瘤表现出改善的肿瘤靶向功效。此前我们开发了铃蟾肽 (BBN)-RGD (Arg-Gly-Asp) 肽异二聚体，其中 BBN 和 RGD 通过不对称谷氨酸接头共价连接 (J Med Chem 52:425–432, 2009)。尽管在共表达胃泌素释放肽受体（GRPR）和整合素αvβ3的PC-3异种移植模型中，18F标记的异二聚体显示出明显优于18F标记的RGD和BBN单体的microPET成像质量，但由于谷氨酸连接体的不对称性质，繁琐的异二聚体合成限制了其临床应用。在本研究中，我们报道了使用对称连接体 AEADP [AEADP = 3,3′-(2-氨基乙基氮烷二基)二丙酸]来合成 BBN-RGD 肽异二聚体。 18F标记的异二聚体(18F-FB-AEADP-BBN-RGD)显示出与谷氨酸连接的BBN-RGD异二聚体相当的microPET成像结果，表明用AEADP连接体替换谷氨酸连接体不会影响BBN-RGD异二聚体的生物活性。异二聚体的合成相当容易和直接。由于肿瘤通常共表达多个受体，因此对称接头的使用提供了快速组装各种肽异二聚体以对表达多受体的肿瘤进行成像的通用方法。
A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425–432, 2009). Although 18F-labeled heterodimers showed significantly better microPET imaging quality than 18F-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin αvβ3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications. In this study, we report the use of a symmetric linker AEADP [AEADP = 3,3′-(2-aminoethylazanediyl)dipropanoic acid] for the synthesis of BBN-RGD peptide heterodimer. The 18F-labeled heterodimer (18F-FB-AEADP-BBN-RGD) showed comparable microPET imaging results with glutamate linked BBN-RGD heterodimers, indicating that the replacement of glutamate linker with AEADP linker did not affect the biological activities of BBN-RGD heterodimer. The heterodimer synthesis is rather easy and straightforward. Because tumors often co-express multiple receptors, the use of a symmetric linker provides a general method of fast assembly of various peptide heterodimers for imaging multi-receptor expressing tumors.
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影响因子：
4.7
作者：
Liu S
通讯作者：
Liu S
DOI：
10.1007/s00259-009-1123-z
发表时间：
2009-09-01
影响因子：
9.1
作者：
Liu, Zhaofei;Niu, Gang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
2.1
作者：
Di Sant'Agnese, PA
通讯作者：
Di Sant'Agnese, PA
影响因子：
3.5
作者：
Yan, Yongjun;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
DOI：
10.1007/s00259-003-1452-2
发表时间：
2004-08-01
影响因子：
9.1
作者：
Chen, XY;Park, R;Conti, PS
通讯作者：
Conti, PS