LOW‐DOSE MONOCLONAL ANTIBODY IMAGING OF NUDE MICE BEARING CEA‐SECRETING XENOGRAFTS
LOW‐DOSE MONOCLONAL ANTIBODY IMAGING OF NUDE MICE BEARING CEA‐SECRETING XENOGRAFTS
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携带 CEA 分泌异种移植物的裸鼠的低剂量单克隆抗体成像
DOI：
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发表时间：
1984
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影响因子：
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通讯作者：
J. Beatty
中科院分区：
文献类型：
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作者：
L. Williams;J. Jakowatz;R. Paxton;D. Porudominsky;B. Clark;B. Beatty;W. G. Vlahos;J. Shively;J. Beatty
癌胚抗原（CEA）的单克隆抗体（MoAb）的生物分布和图像获得在荷LS 174 T人肿瘤的裸鼠模型。使用双功能螯合物用In-111标记的MoAb（T84，66）最初针对人血细胞和肝细胞进行筛选，并且没有显示交叉反应性。使用三种水平的该IgG蛋白：每只动物62.5、625和6250 ngm。比活度为50 nCi/ngm。在IV注射抗CEA MoAb后48小时，每克组织的注射剂量百分比（% ID/gm）如下（平均值± SEM）：62.5 625 6250 ngm LS 174 T 7.0 ± 0.B 11.6 ± 1.8 35.0 ± 6.2血液0.8 ± 0.1 1.3 ± 0.3 6.4 ± 1.4肝脏5.7 ± 0.7 5.7 ± 0.6 13.3 ± 1.5即使在62.5 ngm水平显示肿瘤为明显的活动灶。使用62.5 ngm抗P450 MoAb的对照实验产生6.5 ± 0.5%ID/gm（48 h）的LS 174 T摄取，但肿瘤/血液比（T/B）仅为0.62，而抗CEA为8.8。用抗EMT 6肿瘤的抗CEA的第二对照导致2.4 ± 0.3%ID/gm的肿瘤摄取和T/B = 1.4。我们的结论是，注射62.5 ngm的T84.66单克隆抗体提供了有用的成像CEA分泌肿瘤的裸鼠。这种蛋白质的量，在每千克的基础上，相当于一个成年人的大约200μgm。如此低的剂量可能允许在没有对T84.66鼠抗体的免疫系统应答的情况下进行系列临床研究。
Biodistributions and images of a monoclonal antibody (MoAb) to carcinoembryonic antigen (CEA) were obtained in a nude mouse model bearing the LS174T human tumor. The MoAb (T84,66), labeled with In-111 using a bi-functional chelate, was initially screened against human blood and liver cells and showed no cross-reactivity. Three levels of this IgG protein were used: 62.5, 625 and 6250 ngm per animal. Specific activity was 50 nCi/ngm. Percent injected dose per gram of tissue (% ID/gm) at 48 h post IV injection of the anti-CEA MoAb was as follows (mean ± SEM): 62.5 625 6250 ngm LS174T 7.0 ± 0.B 11.6 ± 1.8 35.0 ± 6.2 Blood 0.8 ± 0.1 1.3 ± 0.3 6.4 ± 1.4 Liver 5.7 ± 0.7 5.7 ± 0.6 13.3 ± 1.5 Imaging at even the 62.5 ngm level revealed the tumor as a distinct focus of activity. A control experiment using 62.5 ngm of anti-P450 MoAb yielded a LS174T uptake of 6.5 ± 0.5 % ID/gm (48 h), but with a tumor/blood ratio (T/B) of only 0.62 as compared to 8.8 for the anti-CEA. A second control with anti-CEA against EMT6 tumor resulted in tumor uptake of 2.4 ± 0.3 % ID/gm and T/B = 1.4. We conclude that an injection of 62.5 ngm of T84.66 MoAb provides useful imaging of CEA-secreting tumors in the nude mouse. This amount of protein is, on a per-kilogram basis, equivalent to approximately 200μgm for an adult human. Such a low dose would probably permit serial clinical studies without immune system response to the T84.66 murine antibody.