64Cu-labeled somatostatin analogues conjugated with cross-bridged phosphonate-based chelators via strain-promoted click chemistry for PET imaging: in silico through in vivo studies.
64Cu-labeled somatostatin analogues conjugated with cross-bridged phosphonate-based chelators via strain-promoted click chemistry for PET imaging: in silico through in vivo studies.
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64Cu 标记的生长抑素类似物通过应变促进的点击化学与基于交桥膦酸盐的螯合剂缀合，用于 PET 成像：通过计算机模拟进行体内研究。
DOI：
10.1021/jm500416f
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发表时间：
2014-07-24
影响因子：
7.3
通讯作者：
Anderson CJ
中科院分区：
文献类型：
--
作者：
Cai Z;Ouyang Q;Zeng D;Nguyen KN;Modi J;Wang L;White AG;Rogers BE;Xie XQ;Anderson CJ
生长抑素受体亚型2(SSTR2)是一种G蛋白偶联受体，在神经内分泌肿瘤中高表达。建立了SSTR2的同源模型，并利用该模型辅助设计了含膦酸类交叉桥联的新型生长抑素类似物，以评价其作为PET显像剂的可行性。新一代螯合剂通过生物正交、应变促进的炔叠氮环加成反应(SPAAC)与酪氨酸八氢曲酸酯(Y3-Tate)偶联，生成CB-TE1A1P-DBCO-Y3-Tate(AP)和CB-TE1K1P-PEG4-DBCO-Y3-Tate(KP)，与标准的直接偶联方法相比，产率更高。与对接研究一致，点击的生物偶联物与SSTR2显示出高的结合亲和力，Kd值在0.6-2.3 nM之间。选择点击产物的异构体，用于生物分布和PET/CT成像。在AP中引入体积较大的二苯并环辛炔基团可降低循环清除率。然而，来自KP结合物的额外的羧酸基和聚乙二醇键显著改善了铜配合物的标记条件和体内稳定性，并改善了点击的生长抑素类似物较慢的药代动力学。
Somatostatin receptor subtype 2 (sstr2) is a G-protein-coupled receptor (GPCR) that is overexpressed in neuroendocrine tumors. The homology model of sstr2 was built and was used to aid the design of new somatostatin analogues modified with phosphonate-containing cross-bridged chelators for evaluation of using them as PET imaging radiopharmaceuticals. The new generation chelators were conjugated to Tyr3-octreotate (Y3-TATE) through bioorthogonal, strain-promoted alkyne azide cycloaddition (SPAAC) to form CB-TE1A1P–DBCO–Y3-TATE (AP) and CB-TE1K1P–PEG4–DBCO–Y3-TATE (KP) in improved yields compared to standard direct conjugation methods of amide bond formation. Consistent with docking studies, the clicked bioconjugates showed high binding affinities to sstr2, with Kd values ranging from 0.6 to 2.3 nM. Selected isomers of the clicked products were used in biodistribution and PET/CT imaging. Introduction of the bulky dibenzocyclooctyne group in AP decreased clearance rates from circulation. However, the additional carboxylate group and PEG linker from the KP conjugate significantly improved labeling conditions and in vivo stability of the copper complex and ameliorated the slower pharmacokinetics of the clicked somatostatin analogues.
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影响因子：
3.5
作者：
Constantinescu CC;Mukherjee J
通讯作者：
Mukherjee J
影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
DOI：
10.1039/c1dt11743b
发表时间：
2012-02-21
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
Ferdani R;Stigers DJ;Fiamengo AL;Wei L;Li BT;Golen JA;Rheingold AL;Weisman GR;Wong EH;Anderson CJ
通讯作者：
Anderson CJ
影响因子：
15
作者：
Boren, Brant C.;Narayan, Sridhar;Fokin, Valery V.
通讯作者：
Fokin, Valery V.
影响因子：
3.5
作者：
Kemp BJ;Hruska CB;McFarland AR;Lenox MW;Lowe VJ
通讯作者：
Lowe VJ