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基于赖氨酸-树枝状接枝大分子的新型纳米生物相容性磁共振对比剂。

New nanosized biocompatible MR contrast agents based on lysine-dendri-graft macromolecules.

机构信息

Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institute of Health, Research Technology Program, SAIC-Frederick, Inc., NCI-Frederick, USA.

出版信息

Bioconjug Chem. 2010 May 19;21(5):955-60. doi: 10.1021/bc9005442.

DOI:10.1021/bc9005442
PMID:20235572
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2884170/
Abstract

Paramagnetic nanomaterials for use as magnetic resonance imaging (MRI) contrast agents have higher relaxivity than conventional low molecular weight MRI agents. However, the biocompatibility and pharmacokinetics of such nanomaterials will strongly affect the likelihood of clinical approval. We synthesized MRI contrast agents based on biocompatible lysine-dendri-grafts: Gd-BzDTPA-lysineG2 and Gd-BzDTPA-lysineG3. The relaxivity of Gd-BzDTPA-lysineG2 and Gd-BzDTPA-lysineG3 increased with sample temperature, while the relaxivity of Gd-BzDTPA-PAMAMG4 decreased with increasing sample temperature. The increase in relaxivity with increasing temperature may be attributed to accessibility of water to the internal Gd chelates with lysine-dendri-grafts, which does not occur with PAMAM dendrimers. Gd-BzDTPA-lysineG3 had a long intravascular half-life but were largely excreted by the kidneys. Therefore, Gd-BzDTPA-lysineG3 enhanced the blood vessels for longer periods than Gd-BzDTPA-PAMAMG4, but was still excreted through the kidney. Because of their biocompatibility, desirable magneto-physical characteristics and favorable pharmacokinetics, which are derived from different interior structures rather than the physical size, lysine-dendri-graft MR contrast agents may be feasible for clinical use.

摘要

基于生物相容性赖氨酸树枝状大分子的 MRI 对比剂的合成及其弛豫性能研究

具有超顺磁性的纳米材料可用作磁共振成像（MRI）对比剂，其弛豫率高于传统的低相对分子质量 MRI 对比剂。然而，此类纳米材料的生物相容性和药代动力学将强烈影响其获得临床批准的可能性。我们合成了基于生物相容性赖氨酸树枝状大分子的 MRI 对比剂：Gd-BzDTPA-lysineG2 和 Gd-BzDTPA-lysineG3。Gd-BzDTPA-lysineG2 和 Gd-BzDTPA-lysineG3 的弛豫率随样品温度升高而升高，而 Gd-BzDTPA-PAMAMG4 的弛豫率随样品温度升高而降低。随着温度的升高，弛豫率的增加可能归因于具有赖氨酸树枝状大分子的内部 Gd 螯合物与水的可及性增加，而这在 PAMAM 树枝状大分子中不会发生。Gd-BzDTPA-lysineG3 具有较长的血管内半衰期，但主要通过肾脏排泄。因此，Gd-BzDTPA-lysineG3 增强血管的时间长于 Gd-BzDTPA-PAMAMG4，但仍通过肾脏排泄。由于其生物相容性、理想的磁物理特性和良好的药代动力学特性，这些特性源于不同的内部结构，而不是物理尺寸，赖氨酸树枝状大分子 MRI 对比剂可能适用于临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/e271cb0865f0/nihms188987f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/1773d2133003/nihms188987f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/96d425ea5625/nihms188987f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/c2f6239f6602/nihms188987f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/2617f27a900f/nihms188987f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/edfd39b18619/nihms188987f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/e271cb0865f0/nihms188987f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/1773d2133003/nihms188987f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/96d425ea5625/nihms188987f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/c2f6239f6602/nihms188987f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/2617f27a900f/nihms188987f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/edfd39b18619/nihms188987f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b553/2884170/e271cb0865f0/nihms188987f6.jpg

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