Improving tumor uptake and excretion kinetics of 99mTc-labeled cyclic arginine-glycine-aspartic (RGD) dimers with triglycine linkers.
Improving tumor uptake and excretion kinetics of 99mTc-labeled cyclic arginine-glycine-aspartic (RGD) dimers with triglycine linkers.
复制标题
DOI：
10.1021/jm801134k
复制
发表时间：
2008-12-25
影响因子：
7.3
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Shi J;Wang L;Kim YS;Zhai S;Liu Z;Chen X;Liu S
本文报道了两种新的环RGD （Arg-Gly-Asp）二聚体3 （E[G3-c(RGDfK)]2）和4 （G3-E[G3-c(RGDfK)]2）及其相应的偶联物5 (HYNIC-E[G3-c（RGDfK)]2: HYNIC = 6-（2-（2-磺基苯甲醛）肼）烟碱）和6 （HYNIC-G3-E[G3-c(RGDfK)]2）的合成。整合素αvβ3 5和6的结合亲和力通过125I-echistatin与U87MG胶质瘤细胞的结合位移来测定。以高产率和高比活性制备了99mTc配合物7 ([99mTc（5)（三嗪）（TPPTS）]: TPPTS =三苯基膦-3,3′，3″-三磺酸三钠）和8 ([99mTc（6)（三嗪）（TPPTS）]）。在携带U87MG胶质瘤和MDA-MB-435乳腺癌异种移植物的胸腺裸鼠中进行生物分布和成像研究。研究发现，G3连接体尤其有助于提高环RGD二聚体的整合素αvβ3结合亲和力，并改善其99mTc放射性示踪剂的肿瘤摄取和清除动力学。配合物8是一种非常有前途的放射性示踪剂，可用于早期检测整合素αvβ3阳性肿瘤，并可能在抗血管生成治疗期间无创监测肿瘤生长或收缩。
This report describes the synthesis of two new cyclic RGD (Arg-Gly-Asp) dimers, 3 (E[G3-c(RGDfK)]2) and 4 (G3-E[G3-c(RGDfK)]2), and their corresponding conjugates 5 (HYNIC-E[G3-c(RGDfK)]2: HYNIC = 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinyl) and 6 (HYNIC-G3-E[G3-c(RGDfK)]2). Integrin αvβ3 binding affinities of 5 and 6 were determined by displacement of 125I-echistatin bound to U87MG glioma cells. 99mTc complexes 7 ([99mTc(5)(tricine)(TPPTS)]: TPPTS = trisodium triphenylphosphine-3,3′,3″-trisulfonate) and 8 ([99mTc(6)(tricine)(TPPTS)]) were prepared in high yield and high specific activity. Biodistribution and imaging studies were performed in athymic nude mice bearing U87MG glioma and MDA-MB-435 breast cancer xenografts. It was found that G3 linkers are particularly useful for increasing integrin αvβ3 binding affinity of cyclic RGD dimers, and improving the tumor uptake and clearance kinetic of their 99mTc radiotracers. Complex 8 is a very promising radiotracer for the early detection of integrin αvβ3–positive tumors, and may have the potential for non-invasive monitoring of tumor growth or shrinkage during antiangiogenic treatment.
登录
查看更多内容
影响因子：
3.1
作者：
Chen, XY;Liu, S;Conti, PS
通讯作者：
Conti, PS
影响因子：
2.8
作者：
Chen, Xiaoyuan;Tohme, Michel;Conti, Peter S.
通讯作者：
Conti, Peter S.
影响因子：
4
作者：
Costouros, NG;Diehn, FE;Libutti, SK
通讯作者：
Libutti, SK
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
4.7
作者：
Alves, Susana;Correia, Joao D. G.;Smith, Charles J.
通讯作者：
Smith, Charles J.