钆-乙氧基苄基-二乙三胺五乙酸，一种新型肝脏靶向磁共振造影剂。无急性肝毒性、心血管或免疫原性效应。

Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects.

作者信息

Mühler A, Clément O, Saeed M, Lake J R, Stites D P, Berthezène Y, Brasch R C

机构信息

Contrast Media Laboratory, University of California, San Francisco 94143-0628.

出版信息

Invest Radiol. 1993 Jan;28(1):26-32. doi: 10.1097/00004424-199301000-00008.

DOI:10.1097/00004424-199301000-00008

PMID:8425849

Abstract

RATIONALE AND OBJECTIVES

Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited.

METHODS

The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB-DTPA using detection of specific antibodies.

RESULTS

Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB-DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3-0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB-DTPA in the intact rat.

CONCLUSIONS

The results further support preliminary conclusions that Gd-EOB-DTPA is a well-tolerated MR contrast agent.

摘要

原理与目的

钆-乙氧基苄基-DTPA（Gd-EOB-DTPA）是一种最近引入用于肝脏成像的实验性磁共振（MR）造影剂。尽管已经在许多动物模型中研究了肝脏增强情况，但对Gd-EOB-DTPA注射的耐受性评估有限。

方法

作者在离体灌注大鼠肝脏模型中研究急性肝毒性，在麻醉大鼠中研究心血管效应，并通过检测特异性抗体来研究Gd-EOB-DTPA的潜在免疫原性。

结果

使用灌注大鼠肝脏模型，将Gd-EOB-DTPA与对照相比，在功能参数、肝酶或钾释放方面未观察到显著差异，但存在显著的利胆作用（胆汁流量增加250%）。在股静脉推注后观察到Gd-EOB-DTPA的血流动力学效应，但仅在相对高剂量（0.3-0.5 mmol/kg，是人类可能临床剂量的10倍）时出现。在理想的诱导抗体实验条件下，完整大鼠对Gd-EOB-DTPA未产生IgG免疫反应。