Conjugation effects of various linkers on Gd(III) MRI contrast agents with dendrimers: optimizing the hydroxypyridinonate (HOPO) ligands with nontoxic, degradable esteramide (EA) dendrimers for high relaxivity.
Conjugation effects of various linkers on Gd(III) MRI contrast agents with dendrimers: optimizing the hydroxypyridinonate (HOPO) ligands with nontoxic, degradable esteramide (EA) dendrimers for high relaxivity.
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DOI：
10.1021/ja110582e
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发表时间：
2011-03-02
影响因子：
15
通讯作者：
Raymond KN
中科院分区：
文献类型：
--
作者：
Floyd WC 3rd;Klemm PJ;Smiles DE;Kohlgruber AC;Pierre VC;Mynar JL;Fréchet JM;Raymond KN
对于更灵敏的基于钆的磁共振成像（MRI）造影剂，一个关键要求是减缓钆（III）离子的分子翻滚，这会提高钆的弛豫率，即加速附近水分子的核磁共振弛豫的能力。实现这一点的一种途径是与高分子量聚合物（如树枝状大分子）结合。在这项工作中，合成了胺官能化的TREN - 双（1,2 - HOPO）- TAM - 乙胺和TREN - 双（1 - Me - 3,2 - HOPO）- TAM - 乙胺配体，并将它们连接到生物相容性的40 kDa酯酰胺（EA）和基于聚 - L - 赖氨酸（PLL）的树枝状大分子上，这些树枝状大分子能够结合多达八个钆配合物。在37°C时，这些共轭物每个钆的T1弛豫率高达38.14 ± 0.02 mM⁻¹s⁻¹，相当于每个树枝状大分子分子的弛豫率高达228 mM⁻¹s⁻¹。以“每个钆”为基础表示的这种弛豫率是小分子配合物的数倍，且比目前的商业试剂高一个数量级。由于它们的高性能和低毒性，这些大分子可能成为对现有基于钆（III）的造影剂具有吸引力的补充。
One essential requirement for more sensitive gadolinium-based MRI contrast agents is to slow the molecular tumbling of the gadolinium(III) ion, which increases the gadolinium's relaxivity, or the ability to speed up the NMR relaxation of nearby water molecules. One route to this is through conjugation to high-molecular weight polymers such as dendrimers. In this work, amine functionalized TREN-bis(1,2-HOPO)-TAM-ethylamine and TREN-bis(1-Me-3,2-HOPO)-TAM-ethylamine ligands have been synthesized and attached to biocompatible 40 kDa esteramide (EA) and poly-l-lysine based (PLL) dendrimers capable of binding up to eight gadolinium complexes. These conjugates have T1 relaxivities of up to 38.14 ± 0.02 mM-1s-1 per gadolinium at 37 °C, corresponding to relaxivities of up to 228 mM-1s-1 per dendrimer molecule. This relaxivity expressed on a “per Gd” basis is several times that of the small molecule complexes, and an order of magnitude higher than that of current commercial agents. Due to their high performance and low toxicity these macromolecules may constitute an attractive complement to currently available gadolinium(III) based contrast agents.
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影响因子：
3.5
作者：
Nwe, K.;Bernardo, M.;Regino, C. A. S.;Williams, M.;Brechbiel, M. W.
通讯作者：
Brechbiel, M. W.
影响因子：
4.3
作者：
Ali, M. Meser;Woods, Mark;Sherry, A. Dean
通讯作者：
Sherry, A. Dean
影响因子：
18.3
作者：
Datta A;Raymond KN
通讯作者：
Raymond KN
影响因子：
15
作者：
Pierre, VC;Botta, M;Raymond, KN
通讯作者：
Raymond, KN
影响因子：
19.7
作者：
Lauffer, RB;Parmelee, DJ;Walovitch, RC
通讯作者：
Walovitch, RC