Midoux P, Maillet T, Thérain F, Monsigny M, Roche A C
Cancer Immunol Immunother. 1984;18(1):19-23. doi: 10.1007/BF00205394.
Mouse 6D6 IgG2a and 5B5 IgM monoclonal antibodies which specifically bind murine lung carcinoma cells (3LL cells) were injected to healthy and tumor-bearing mice. In vivo localization was analyzed by counting the tissue radioactivity and by external gamma ray scintigraphy at various times after IV injection of 125I- or 131I-labeled antibodies. The clearance of the two monoclonal antibodies was not modified by the presence of the tumor, and the 6D6 IgG2a was cleared at a rate slower than the 5B5 IgM. Both antibodies gave a high specific uptake at the tumor level; the tumor-to-healthy tissue ratios were higher with the 6D6 IgG2a than the 5B5 IgM; unspecific mouse immunoglobulins (IgG2) did not localize in the tumor. The amount of 6D6 IgG2a antibody still associated with the tumor after 2 days following IV injection was 10 times higher than that of 5B5 IgM, and was still high enough to localize the tumor after 5 days. Imaging experiments confirmed the ability of 6D6 IgG2a to detect the presence of tumor cells. The targeting kinetics determined by computer analysis of camera images indicated a rapid targeting of antibodies in tumor with a maximal concentration after 4-6 h; after 48 h the background was quite low and the 6D6 IgG2a appeared to be specifically localized in the tumor.
将特异性结合小鼠肺癌细胞(3LL细胞)的小鼠6D6 IgG2a和5B5 IgM单克隆抗体注射到健康小鼠和荷瘤小鼠体内。静脉注射125I或131I标记的抗体后,在不同时间通过计数组织放射性和外部γ射线闪烁扫描分析体内定位。两种单克隆抗体的清除率不受肿瘤存在的影响,且6D6 IgG2a的清除速率比5B5 IgM慢。两种抗体在肿瘤部位均有较高的特异性摄取;6D6 IgG2a的肿瘤与健康组织比值高于5B5 IgM;非特异性小鼠免疫球蛋白(IgG2)不在肿瘤中定位。静脉注射2天后,与肿瘤仍结合的6D6 IgG2a抗体量比5B5 IgM高10倍,且在5天后仍足以定位肿瘤。成像实验证实了6D6 IgG2a检测肿瘤细胞存在的能力。通过计算机分析相机图像确定的靶向动力学表明,抗体在4-6小时后迅速靶向肿瘤并达到最大浓度;48小时后背景很低,6D6 IgG2a似乎特异性定位于肿瘤中。