A Triazacyclononane-Based Bifunctional Phosphinate Ligand for the Preparation of Multimeric 68Ga Tracers for Positron Emission Tomography
A Triazacyclononane-Based Bifunctional Phosphinate Ligand for the Preparation of Multimeric 68Ga Tracers for Positron Emission Tomography
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DOI：
10.1002/chem.200903281
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Lukes, Ivan
中科院分区：
文献类型：
--
作者：
Notni, Johannes;Hermann, Petr;Lukes, Ivan
用于正电子发射断层扫描（PET）。PrP 9是一种具有甲基（2-羧乙基）次膦酸侧臂的N，N '，N“-三取代三氮杂环壬烷，可作为Ga-68（3+）的配位剂。合成过程短，成本低。Ga-III和Fe-III配合物的PrP 9，其特征在于通过单晶X-射线衍射。用电位法测定了金属配合物的逐步质子化常数和热力学稳定性。Ga-Ⅲ配合物具有较高的热力学稳定性（log K-[GaL]=26.24）和较高的动力学惰性。PrP 9的Ga-68标记可以在环境温度和宽pH范围内进行，甚至在低至1的pH值下进行。这意味着第一次，基于TiO 2的Ge-68/Ga-68发生器（通常由0.1m HCl组成）的纯固体可直接用于标记目的。在pH 3.3和20 ℃下Ga-68活性掺入的速率高于已建立的螯合剂DOTA和NOTA。合成了PrP 9与氨基酸酯的三酰胺，以作为多聚体肽缀合物的模型。这些缀合物表现出与未取代的PrP 9类似的放射性标记性质。
For application in positron emission tomography (PET). PrP9, a N,N',N ''-trisubstituted triazacyclononane with methyl(2-carboxyethyl)phosphinic acid pendant arms, was developed as Ga-68(3+) complexing agent. The synthesis is short and inexpensive. Ga-III and Fe-III complexes of PrP9 were characterized by single-crystal X-ray diffraction. Stepwise protonation constants and thermodynamic stabilities of metal complexes were determined by potentiometry. The Ga-III complex possesses a high thermodynamic stability (log K-[GaL]=26.24) and a high degree of kinetic inertness. Ga-68 labeling of PrP9 is possible at ambient temperature and in a wide pH range, also at pH values as low as 1. This means that for the first time, the neat eluate of a TiO2-based Ge-68/Ga-68 generator (typically consisting of 0.1m HCl) can be directly used for labeling purposes. The rate of Ga-68 activity incorporation at pH 3.3 and 20 degrees C is higher than for the established chelators DOTA and NOTA. Tris-amides of PrP9 with amino acid esters were synthesized to act as models for multimeric peptide conjugates. These conjugates exhibit radiolabeling properties similar to those of unsubstituted PrP9.