IMMUNOGENICITY OF GADOLINIUM-BASED CONTRAST AGENTS FOR MAGNETIC-RESONANCE-IMAGING - INDUCTION AND CHARACTERIZATION OF ANTIBODIES IN ANIMALS
IMMUNOGENICITY OF GADOLINIUM-BASED CONTRAST AGENTS FOR MAGNETIC-RESONANCE-IMAGING - INDUCTION AND CHARACTERIZATION OF ANTIBODIES IN ANIMALS
复制标题
DOI：
10.1097/00004424-199112000-00001
复制
发表时间：
1991-12-01
影响因子：
6.7
通讯作者：
BRASCH, RC
中科院分区：
文献类型：
--
作者：
BAXTER, AB;MELNIKOFF, S;BRASCH, RC
为了评估钆基磁共振成像（MRI）造影剂的免疫原性潜力，我们用钆二乙基三胺五乙酸（Gd-DTPA）二聚氨基乙胺和Gd-DTPA与人血清白蛋白、葡聚糖或聚赖氨酸共价连接的方法致敏sd大鼠。通过酶联免疫吸附试验（ELISA）在免疫血清中检测到针对Gd-DTPA的IgG抗体，并通过游离Gd-DTPA二聚胺竞争性抑制抗体结合来证实。人血清白蛋白-(Gd-DTPA)免疫诱导抗血清，在竞争ELISA中，Gd-DTPA二聚胺同时作为孔包被和驱替剂时，具有50%抑制(IC50) = 5.5 × 10(-4) M的单相竞争曲线。Gd-DTPA二聚胺单独诱导的抗血清具有双相竞争曲线，IC50分别为6.5 × 10(-7) M和7.9 × 10(-4) M。暴露于葡聚糖-(Gd-DTPA)或聚赖氨酸-(Gd-DTPA)后获得的抗血清滴度不足以进行鉴定。Gd-DTPA特异性抗体的检测表明，体内蛋白质与半抗原载体偶联物的形成结合。当Gd-DTPA二聚胺在血清中而不是在水中孵育时，所观察到的相关性值增加，这一假设得到了支持。在理想的实验条件下，Gd-DTPA二聚胺和白蛋白-(Gd-DTPA)在大鼠体内具有免疫原性。需要进一步的研究来确定在临床使用中固有的暴露条件下人体对钆螯合物的免疫反应的潜力。
To evaluate the immunogenic potential of gadolinium-based magnetic resonance imaging (MRI) contrast agents, Sprague-Dawley rats were sensitized with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) dimeglumine and with Gd-DTPA covalently linked to either human serum albumin, dextran, or polylysine. IgG antibodies directed against Gd-DTPA were detected in immune sera by an enzyme-linked immunosorbent assay (ELISA), and were confirmed by competitive inhibition of antibody binding using free Gd-DTPA dimeglumine. Antiserum induced by immunization with human serum albumin-(Gd-DTPA) was characterized by a monophasic competition curve with 50% inhibition (IC50) = 5.5 x 10(-4) M when Gd-DTPA dimeglumine was used as both the well-coating and the displacing agent in a competition ELISA. Antiserum induced by Gd-DTPA dimeglumine alone was characterized by a biphasic competition curve with IC50 = 6.5 x 10(-7) M and 7.9 x 10(-4) M. Antisera obtained after exposure to either dextran-(Gd-DTPA) or polylysine-(Gd-DTPA) were of insufficient titer for characterization. The detection of antibodies specific for Gd-DTPA suggests in vivo protein binding with formation of hapten-carrier conjugates. This hypothesis is supported by increased relativity values observed when Gd-DTPA dimeglumine is incubated in serum rather than in water. Gd-DTPA dimeglumine and albumin-(Gd-DTPA) are immunogenic in rats under idealized experimental conditions. Additional studies will be necessary to determine the Potential for immunologic response in humans to gadolinium chelates under conditions of exposure inherent in clinical use.