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使用钆标记单克隆抗体对移植了结肠直肠癌的裸鼠进行磁共振成像研究。

Magnetic resonance imaging studies on nude mice grafted with colorectal adenocarcinoma using gadolinium-labeled monoclonal antibody.

作者信息

Saccavini J C, Curtet C, Bohy J, Tellier C, Bourgoin C, Lhoste J M

机构信息

Oris Industrie, Gif sur Yvette, France.

出版信息

Invest Radiol. 1988 Sep;23 Suppl 1:S292-3. doi: 10.1097/00004424-198809001-00064.

Abstract

A monoclonal antibody (Ab) 19.9 specific for colorectal carcinoma was labeled with a high number of gadolinium (Gd) atoms for its potential application as a contrast agent in magnetic resonance imaging (MRI). The DTPA was conjugated to 19.9 Ab via the bicyclic DTPA anhydride method (c. DTPA) using c. DTPA/Ab molar ratios between 5 and 150. The aggregates present in great amount at high c. DTPA/Ab ratios were systematically removed. Then the exact number of DTPA effectively conjugated, the immunoreactivity of the resulting 111In-DTPA-Ab were measured. The number of DTPA conjugated per antibody can be increased 20 to 25 with only a little loss of immunoreactivity. The 19.9 antibody conjugated with 16 and 25 DTPA was labeled with 153GdCl3 for pharmacokinetic studies on xenografted nude mice and with nonradioactive gadolinium to measure ex vivo the effect on the relaxation time T1 of the tumor. We found a 15 to 20% decrease of T1 on the tumor. In vivo experiments using a Bruker system and the same animal model showed a difference in the tumor contrast after the injection of 2 mg of Gd-labeled Ab.

摘要

一种对结直肠癌具有特异性的单克隆抗体(Ab)19.9被标记上大量的钆(Gd)原子,以作为磁共振成像(MRI)中的造影剂进行潜在应用。通过双环二乙三胺五乙酸酐法(c. DTPA),使用5至150之间的c. DTPA/Ab摩尔比,将二乙三胺五乙酸(DTPA)与19.9 Ab偶联。在高c. DTPA/Ab比率下大量存在的聚集体被系统地去除。然后测量有效偶联的DTPA的确切数量以及所得111铟 - DTPA - Ab的免疫反应性。每个抗体偶联的DTPA数量可以增加20至25个,而免疫反应性仅有少量损失。将与16和25个DTPA偶联的19.9抗体用153氯化钆标记,用于对异种移植裸鼠进行药代动力学研究,并使用非放射性钆来离体测量其对肿瘤弛豫时间T1的影响。我们发现肿瘤的T1降低了15%至20%。使用布鲁克系统和相同动物模型进行的体内实验表明,注射2毫克钆标记的Ab后,肿瘤对比度存在差异。

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