Baxter A B, Melnikoff S, Stites D P, Brasch R C
Department of Radiology, University of California, San Francisco 94143-0628.
Invest Radiol. 1991 Dec;26(12):1035-40. doi: 10.1097/00004424-199112000-00001.
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 relaxivity 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.
为评估钆基磁共振成像（MRI）造影剂的免疫原性潜力，用钆二乙烯三胺五乙酸（Gd - DTPA）葡甲胺以及与人类血清白蛋白、葡聚糖或聚赖氨酸共价连接的Gd - DTPA对斯普拉格 - 道利大鼠进行致敏。通过酶联免疫吸附测定（ELISA）在免疫血清中检测针对Gd - DTPA的IgG抗体，并使用游离Gd - DTPA葡甲胺竞争性抑制抗体结合来进行确认。用人血清白蛋白 -（Gd - DTPA）免疫诱导的抗血清在竞争ELISA中，当Gd - DTPA葡甲胺用作包被孔和置换剂时，其特征为单相竞争曲线，50%抑制（IC50）= 5.5×10⁻⁴ M。单独用Gd - DTPA葡甲胺诱导的抗血清特征为双相竞争曲线，IC50 = 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）后获得的抗血清效价不足以进行表征。对Gd - DTPA特异性抗体的检测表明体内存在蛋白质结合并形成半抗原 - 载体缀合物。当Gd - DTPA葡甲胺在血清而非水中孵育时观察到的弛豫率值增加支持了这一假设。在理想化实验条件下，Gd - DTPA葡甲胺和白蛋白 -（Gd - DTPA）在大鼠中具有免疫原性。需要进行更多研究以确定在临床使用中固有暴露条件下人类对钆螯合物产生免疫反应的可能性。
