In vivo kinetics of radiolabeled monoclonal anti-CEA antibodies in animal models.
In vivo kinetics of radiolabeled monoclonal anti-CEA antibodies in animal models.
复制标题
动物模型中放射性标记单克隆抗 CEA 抗体的体内动力学。
作者：
P. Hagan;S. Halpern;A. Chen;L. Krishnan;J. Frincke;R. Bartholomew;G. David;D. Carlo
进行研究以确定放射性标记和循环癌胚抗原（CEA）对单克隆抗CEA抗体（MoAb）的药效学的影响。在正常BALB/c小鼠和荷人结肠肿瘤的裸鼠中进行研究。使用了三种不同的肿瘤，每种肿瘤产生的CEA水平都是该特定肿瘤分泌速率的特征。在所有研究中均使用111 In或125 I标记的CEJ-326单克隆抗体。循环CEA诱导125 I和111 In单克隆抗体从血管室中清除。随着肿瘤CEA分泌率的升高，肝脏111 In浓度升高，125 I浓度降低。这表明循环CEA复合物在血管区室中形成，其在动物模型中被肝脏和脾脏去除。这导致标记的MoAb的肿瘤摄取减少。碘化的单克隆抗体复合物被脱卤，而111 In被肝脏保留。这种脱卤作用可以解释在使用完整的放射性碘标记的抗CEA单克隆抗体的放射免疫成像中观察到的相对较低的肝脏活性，前提是CEA复合物类似地被人肝脏从血管隔室中去除。
Studies were performed to determine the effect of the radiolabel and circulating carcinoembryonic antigen (CEA) on the pharmacodynamics of monoclonal anti-CEA antibodies (MoAbs). The studies were performed in normal BALB/c mice and in nude mice bearing human colon tumors. Three different tumors were used, each of which produced CEA levels characteristic of that particular tumor's secretory rate. The CEJ-326 MoAb labeled with either 111In or 125I was used in all studies. Circulating CEA induced the removal of 125I and 111In MoAbs from the vascular compartment. Liver concentrations of 111In increased and 125I levels decreased as the CEA secretory rate of the tumor rose. This indicates that circulating CEA complexes form in the vascular compartment which, in an animal model, are removed by the liver and spleen. This results in decreased tumor uptake of the labeled MoAb. The iodinated MoAb complexes are dehalogenated while the 111In is retained by the liver. This dehalogenation may account for the relatively low liver activity observed in radioimmunoimaging with intact radioiodinated anti-CEA MoAbs, provided the CEA complexes are similarly removed from the vascular compartment by the human liver.