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使用与单克隆抗体19-9偶联的钆-二亚乙基三胺五乙酸对人结肠直肠癌中核磁共振弛豫时间进行选择性修饰。

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

作者信息

Curtet C, Tellier C, Bohy J, Conti M L, Saccavini J C, Thedrez P, Douillard J Y, Chatal J F, Koprowski H

出版信息

Proc Natl Acad Sci U S A. 1986 Jun;83(12):4277-81. doi: 10.1073/pnas.83.12.4277.

Abstract

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors.

摘要

将抗人结肠腺癌的单克隆抗体19-9(mAb 19-9)与钆二乙烯三胺五乙酸(Gd X DTPA)偶联,并用作核磁共振(NMR)中的造影剂,以提高裸鼠体内肿瘤靶向选择性。数据表明,溶液中的Gd X DTPA-mAb 19-9以与钆浓度成正比的方式降低了90 MHz时水质子的T1弛豫,且这种效应大于Gd X DTPA溶液中的效应。在注射Gd X DTPA-mAb 19-9(钆,20 μmol/kg;每mAb分子含16个DTPA分子)24小时后从裸鼠体内取出的肿瘤中测量的90 MHz时的T1弛豫时间与对照组相比显著降低(降低了15%)。在用2、6或10 μmol/kg钆(每mAb分子含16个DTPA分子)的Gd X DTPA-mAb 19-9溶液注射的小鼠肿瘤中也得到了类似结果。这些剂量低于通常用作造影剂的Gd X DTPA的剂量(10 - 100 μmol/kg)。含有放射性钆(0.3 μCi/μg的153Gd)的Gd X DTPA-mAb 19-9复合物用于肿瘤定位以确认闪烁扫描,结果显示肿瘤中复合物浓度显著(每克组织中为注射剂量的5%)。第5天平面闪烁扫描记录的扫描图像显示肿瘤可视化良好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10c6/323715/cb7582e4d96b/pnas00316-0180-a.jpg

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