钆-C4-甲状腺素-DTPA 的合成及理化性质表征，一种潜在的 MRI 对比剂。通过质子弛豫率、NMR 扩散度和电喷雾质谱评估其与人血清白蛋白的亲和力。

Synthesis and physicochemical characterization of Gd-C4-thyroxin-DTPA, a potential MRI contrast agent. Evaluation of its affinity for human serum albumin by proton relaxometry, NMR diffusometry, and electrospray mass spectrometry.

机构信息

Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 19 avenue Maistriau, B-7000 Mons, Belgium.

出版信息

J Phys Chem B. 2010 Mar 18;114(10):3689-97. doi: 10.1021/jp910961j.

DOI:10.1021/jp910961j

PMID:20175550

Abstract

Gd-C(4)-thyroxin-DTPA, a potential MRI contrast agent, was synthesized from Gd-DTPA and thyroxine, which interacts strongly with human serum albumin (HSA). It was characterized in water by its relaxometric properties and its stability versus zinc transmetalation. The affinity of the complex for HSA was studied by using three different methods: proton relaxometry, NMR diffusometry, and electrospray mass spectrometry. From the results, it appears that Gd-C(4)-thyroxin-DTPA exhibits a relatively high relaxivity (r(1) = 9.01 s(-1) mM(-1) at 1.5 T and 310 K), a good stability versus zinc transmetalation, and a strong interaction with HSA (K(a) approximately 10,000 M(-1) with two binding sites). The kinetics of the exchange between the bound and the free form of the complex was evaluated by the NMR diffusometry technique. Competition experiments have allowed the assignment of the chelate's binding site on HSA.

摘要

Gd-C(4)-甲状腺素-DTPA 是一种潜在的 MRI 造影剂，由 Gd-DTPA 和甲状腺素合成，与人体血清白蛋白（HSA）强烈相互作用。它在水中的弛豫特性及其对锌转金属化的稳定性通过弛豫率特性进行了表征。该复合物与 HSA 的亲和力通过三种不同的方法进行了研究：质子弛豫率法、NMR 扩散率法和电喷雾质谱法。结果表明，Gd-C(4)-甲状腺素-DTPA 表现出相对较高的弛豫率（在 1.5 T 和 310 K 时 r(1) = 9.01 s(-1) mM(-1)），对锌转金属化具有良好的稳定性，与 HSA 具有很强的相互作用（K(a)约为 10,000 M(-1)，有两个结合位点）。通过 NMR 扩散率技术评估了复合物结合形式和游离形式之间的交换动力学。竞争实验允许对 HSA 上螯合物的结合位点进行分配。