Monoclonal antibody A7-superparamagnetic iron oxide as contrast agent of MR imaging of rectal carcinoma.

Monoclonal antibody A7-superparamagnetic iron oxide as contrast agent of MR imaging of rectal carcinoma.
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DOI:
10.1038/sj.bjc.6602668
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发表时间:
2005-07-11
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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超顺磁性氧化铁(SPIO)胶体已作为组织特异性磁共振造影剂应用于临床。我们将与人结直肠癌特异反应的单抗A7(Mab A7)偶联到阿魏酸铁(Ferumoxide,SPIO)上,并检测了这种结合物在裸鼠移植瘤中的蓄积。我们检测了单抗A7与亚铁氧化物偶联的体外免疫反应性及其在裸鼠体内的分布。注射A7-亚铁氧化物72 h后,对荷瘤裸鼠进行磁共振成像。A7-亚铁氧化物保留了与完整的单抗A7几乎相同的结合活性。从注射后12 小时起,放射性标记的A7-Ferumoxide在肿瘤中的积聚多于正常小鼠的Ig G-Ferumoxide(P<0.05)。随着时间的推移,A7-亚铁氧化物和正常小鼠的免疫球蛋白亚铁氧化物都线性地从血液中消失。在正常组织中的蓄积水平随着时间的推移呈线性下降,但从6 h开始低于在肿瘤中的水平。在荷瘤裸鼠的磁共振T2加权成像中,注射A7-亚铁氧化物使肿瘤边缘的信号强度降低。单抗A7与亚铁氧化物偶联可作为检测直肠癌局部复发的磁共振造影剂。
Superparamagnetic iron oxide (SPIO)-based colloid has been used clinically as a tissue-specific magnetic resonance contrast agent. We coupled monoclonal antibody A7 (Mab A7), which reacts specifically with human colorectal carcinoma, to Ferumoxides (SPIO) and examined the accumulation of this conjugate in xenografted tumours in nude mice. We examined in vitro immunoreactivity of Mab A7 coupled to Ferumoxides and its in vivo distribution in nude mice with human colorectal carcinoma. Magnetic resonance imaging of tumour-bearing nude mice was performed 72 h after injection of A7-Ferumoxides. A7-Ferumoxides retained binding activities that were nearly identical to intact Mab A7. More of the radiolabelled A7-Ferumoxides accumulated in the tumour than normal mouse IgG-Ferumoxides from 12 h onwards after injection (P<0.05). Both A7-Ferumoxides and normal mouse IgG-Ferumoxides disappeared from blood linearly over time. The accumulation levels in normal tissue decreased linearly over time but were lower than levels in tumours from 6 h. In magnetic resonance T2-weighted imaging of the tumour-bearing nude mice, signal intensity was reduced at the margin of the tumour by injection of A7-Ferumoxides. Mab A7 coupled to Ferumoxides is potentially suitable as a magnetic resonance contrast agent for detecting local recurrence of rectal carcinoma.
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