Hak Sjoerd, Sanders Honorius M H F, Agrawal Prashant, Langereis Sander, Grüll Holger, Keizer Henk M, Arena Francesca, Terreno Enzo, Strijkers Gustav J, Nicolay Klaas
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Eur J Pharm Biopharm. 2009 Jun;72(2):397-404. doi: 10.1016/j.ejpb.2008.09.017. Epub 2008 Oct 10.
The field of molecular imaging aims to visualize and quantify (patho)physiological processes at the cellular and molecular level. Sensitive and site-targeted contrast agents are employed to visualize molecular constituents of processes of interest. The principal aim of this study was to develop a magnetic resonance imaging (MRI) detectable liposome with high relaxivity and stability. To this end, Gd(III)DOTA-DSPE was synthesized and incorporated in a liposomal formulation. The resulting liposomes were extensively characterized in vitro in terms of contrast agent efficiency and structural properties. The liposomes were shown to have a high longitudinal relaxivity, which is crucial for the detection of low concentration molecular markers in molecular imaging studies. We also demonstrated that Gd(III)DOTA-DSPE exhibits no detectable transmetallation upon incubation with Zn(II). This is important as it significantly contributes to the biocompatibility of the contrast agent. The present liposome preparation will serve as versatile and well characterized platform for molecular imaging and targeted drug delivery studies.
分子成像领域旨在在细胞和分子水平上可视化和量化（病理）生理过程。使用灵敏且靶向定位的造影剂来可视化感兴趣过程的分子成分。本研究的主要目的是开发一种具有高弛豫率和稳定性的磁共振成像（MRI）可检测脂质体。为此，合成了钆（III）-二乙三胺五乙酸-二硬脂酰基磷脂酰乙醇胺（Gd(III)DOTA-DSPE）并将其掺入脂质体制剂中。所得脂质体在体外就造影剂效率和结构特性进行了广泛表征。这些脂质体显示出高纵向弛豫率，这对于分子成像研究中低浓度分子标记物的检测至关重要。我们还证明，钆（III）-二乙三胺五乙酸-二硬脂酰基磷脂酰乙醇胺（Gd(III)DOTA-DSPE）与锌（II）孵育时未表现出可检测到的金属离子转移。这很重要，因为它对造影剂的生物相容性有显著贡献。目前的脂质体制备将作为用于分子成像和靶向药物递送研究的通用且特性良好的平台。
