In vivo evaluation of gadolinium hydroxypyridonate chelates: Initial experience as contrast media in magnetic resonance imaging

被引：30

作者：

Thompson, MK

Misselwitz, B

Tso, LS

Doble, DMJ

Schmitt-Willich, H

Raymond, KN ^{[1
]}

机构：

[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[2] Schering AG, Res Labs, D-13342 Berlin, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 11期

关键词：

D O I：

10.1021/jm049041m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The effect of ligand structure on the magnetic resonance (MR) imaging and biodistribution of six gadolinium (Gd) chelates based on a hydroxypyridonate-terephthalimide (HOPO-TAM) ligand design was investigated. Modifications to the molecular structure of the Gd-HOPO-TAM chelates (hydrophilicity and aromatic group substitution) significantly influence the efficacy of imaging and biodistribution. MR imaging was performed on female mice after intravenous (iv) injection of 100 mu mol of Gd/kg of body weight of the different complexes. The biodistribution results indicate that the liver uptake of the complexes is enhanced by a short poly(ethyleneoxy) (PEO) chain, while blood pool localization is facilitated by a very long PEO chain. There is a direct correlation between the blood pool localization of the complexes and the signal intensity of blood vessels in the MRI. The imaging results are consistent with in vitro NMR measurements that indicate long PEO chains increase image enhancement capabilities in the presence of serum albumin.

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页码：3874 / 3877

页数：4

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