Gadolinium MRI contrast agents based on triazine dendrimers: relaxivity and in vivo pharmacokinetics.
Gadolinium MRI contrast agents based on triazine dendrimers: relaxivity and in vivo pharmacokinetics.
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DOI：
10.1021/bc300461r
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发表时间：
2012-11-21
影响因子：
4.7
通讯作者：
Kobayashi, Hisataka
中科院分区：
文献类型：
--
作者：
Lim, Jongdoo;Turkbey, Baris;Bernardo, Marcelino;Bryant, L. Henry, Jr.;Garzoni, Matteo;Pavan, Giovanni M.;Nakajima, Takahito;Choyke, Peter L.;Simanek, Eric E.;Kobayashi, Hisataka
制备了四种基于钆（Gd）的大分子造影剂，G3-（Gd-DOTA）24、G5-（Gd-DOTA）96、G3-（Gd-DTPA）24和G5-（Gd-DTPA）96，它们在树枝状聚合物的尺寸（第三代和第五代）、螯合基团的类型（DTPA或DOTA）和金属化螯合物的理论数量（24和96）方面不同。合成依赖于用DOTA或DTPA配体衍生的二氯三嗪，将其掺入树枝状聚合物中并最终用Gd离子金属化。研究了所有四种造影剂的顺磁特性和体内药代动力学。含DOTA的试剂G3-（Gd-DOTA）24和G5-（Gd-DOTA）96在非峰值磁场下表现出异常高的r1弛豫率值。此外，G5-（Gd-DOTA）96在血清中显示出比在PBS中增加的r1弛豫率，这与体内图像一致。虽然G3-（Gd-DOTA）24和G3-（Gd-DTPA）24被迅速排泄到尿液中，但G5-（Gd-DOTA）96和G5-（Gd-DTPA）96并不快速通过肾脏清除。含DOTA的树枝状聚合物的分子模拟提供了结构的单分子水平表征，并表明大多数金属化配体可接近水。这些三嗪树枝状聚合物为基础的MRI造影剂表现出几个有前途的功能，如高的体内r1弛豫，理想的药代动力学，以及明确的结构。
Four gadolinium (Gd)-based macromolecular contrast agents, G3-(Gd-DOTA)24, G5-(Gd-DOTA)96, G3-(Gd-DTPA)24, and G5-(Gd-DTPA)96, were prepared that varied in the size of dendrimer (generation three and five), the type of chelate group (DTPA or DOTA), and the theoretical number of metallated chelates (24 and 96). Synthesis relied on a dichlorotriazine derivatized with a DOTA or DTPA ligand that was incorporated into the dendrimer and ultimately metallated with Gd ions. Paramagnetic characteristics and in vivo pharmacokinetics of all four contrast agents were investigated. The DOTA-containing agents, G3-(Gd-DOTA)24 and G5-(Gd-DOTA)96, demonstrated exceptionally high r1 relaxivity values at off peak magnetic fields. Additionally, G5-(Gd-DOTA)96 showed increased r1 relaxivity in serum compared to that in PBS, which was consistent with in vivo images. While G3-(Gd-DOTA)24 and G3-(Gd-DTPA)24 were rapidly excreted into the urine, G5-(Gd-DOTA)96 and G5-(Gd-DTPA)96 did not clear as quickly through the kidneys. Molecular simulation of the DOTA-containing dendrimers provides a single-molecular level characterization of the structures and suggests that a majority of the metallated ligands are accessible to water. These triazine dendrimer-based MRI contrast agents exhibit several promising features such as high in vivo r1 relaxivity, desirable pharmacokinetics, and well-defined structure.
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影响因子：
15
作者：
Lim, Jongdoo;Pavan, Giovanni M.;Simanek, Eric E.
通讯作者：
Simanek, Eric E.
基于物理和生物学的下一代分子成像探针的合理化学设计：混合方式，颜色和信号。
影响因子：
46.2
作者：
Kobayashi H;Longmire MR;Ogawa M;Choyke PL
通讯作者：
Choyke PL
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
15
作者：
Garzoni, Matteo;Cheval, Nicolas;Pavan, Giovanni M.
通讯作者：
Pavan, Giovanni M.
影响因子：
4.7
作者：
Longmire, Michelle R.;Ogawa, Mikako;Choyke, Peter L.;Kobayashi, Hisataka
通讯作者：
Kobayashi, Hisataka