Dextran Coated Gadolinium Phosphate Nanoparticles for Magnetic Resonance Tumor Imaging
Dextran Coated Gadolinium Phosphate Nanoparticles for Magnetic Resonance Tumor Imaging
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DOI：
10.1039/b902134e
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Suzuki, Koji
中科院分区：
文献类型：
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作者：
Hifumi, Hiroki;Yamaoka, Seiichi;Suzuki, Koji
肿瘤检测具有很大的临床意义。众所周知，实体瘤具有独特的血管病理生理学特征，总结为术语“增强的渗透性和保留（EPR）效应”，其诱导大分子从血液到肿瘤中的积累和延长的保留。因此，我们设计并合成了葡聚糖包裹的顺磁性磷酸钆纳米颗粒（PGP/葡聚糖）作为一种新的磁共振成像（MRI）造影剂。这种新材料的主要特征是：（i）具有阳性造影剂的特性，可提供更高的成像分辨率，（ii）数十纳米的尺寸可累积并保留在肿瘤中，以及（iii）具有高度生物相容性的葡聚糖涂层，可防止从血流中快速消除。在这篇文章中，我们描述了使用PGP/葡聚糖可视化肿瘤的药代动力学研究、毒性试验和MR成像实验的结果，并将其与临床使用的造影剂Magnevist（R）进行比较。依靠EPR效应，使用颗粒和阳性PGP/葡聚糖在常规T1加权MR图像上成功地可视化了兔子中的肿瘤，与Magenvist（R）相比，其应用剂量仅为1/10。肿瘤的这种有效可视化是PGP/葡聚糖的综合特征的结果，其具有用于MRI的阳性造影剂的足够特征、显著长的血浆半衰期和高生物相容性。PGP/右旋糖酐可用作肿瘤特异性造影剂和将药物递送至肿瘤的载体。
Tumor detection is of great clinical interest. It is known that solid tumors have unique vascular pathophysiological features summarized under the term "enhanced permeability and retention (EPR) effect'', which induces the accumulation and prolonged retention of macromolecules from the blood into the tumor. We therefore have designed and synthesized dextran coated paramagnetic gadolinium phosphate nanoparticles (PGP/dextran) as a new magnetic resonance imaging (MRI) contrast agent. The main features of this new material are: (i) characteristics of a positive contrast agent providing higher imaging resolution, (ii) size of several tens of nanometres to accumulate and to be retained into tumors, and (iii) highly biocompatible dextran coating to prevent the rapid elimination from the blood stream. In this article, we describe the results of pharmacokinetic studies, toxicity tests, and MR imaging experiments to visualize tumors using PGP/dextran, and compare them to the clinically used contrast agent Magnevist (R). Relying on the EPR effect, tumors in a rabbit were successfully visualized on conventional T1-weighted MR images using the particulate and positive PGP/dextran with only 1/10 of the applied dose compared to Magnevist (R). This efficient visualization of a tumor is the result of the comprehensive features of PGP/dextran, having adequate characteristics of a positive contrast agent for MRI, a significantly long plasma half-life and a high biocompatibility. PGP/dextran could be used as a tumor specific contrast agent and as a vehicle to deliver drugs to a tumor.