^131 I—Rituximab对B细胞淋巴瘤生物学效应的实验研究

目的：研究^131 I标记的Rituximab对B细胞淋巴瘤细胞的生物学效应以及对荷人Raji细胞移植瘤裸鼠的放射免疫治疗效果，为放射免疫导向治疗提供实验依据。方法：体外培养人B细胞淋巴瘤细胞系Raji细胞，裸鼠皮下接种Raji细胞成瘤，IODO-GEN法将^131 I标记于Rituximab，将细胞分为^131 I—Rituximab组、单纯抗体组、单纯核素组及空白对照组4组，流式细胞仪检测各组Raji细胞凋亡和细胞周期；取30只成瘤裸鼠随机分成高、中、低剂量治疗组及单纯抗体组、单纯核素组、空白对照组6组，进行裸鼠的放射免疫治疗研究。每周测量裸鼠荷瘤大小1次，4周后处死裸鼠，取瘤称重，常规病理分析。结果：^131 I．Rituximab组凋亡率高于其他各组；^131 I—Rituximab组细胞周期发生变化，大部分被阻滞在G2期。裸鼠各治疗组与对照组比较，肿瘤生长减慢，肿瘤生长抑制率具有剂量时间依赖性，组织病理学检测显示治疗有效。结论：^131 I—Rituximab能够诱导Raji细胞凋亡并调控细胞周期，而且可特异性地定位于肿瘤组织，发挥放射免疫导向治疗作用，具有潜在的临床应用价值。

Biological response of B-cell lymphoma to ^131 I-Rituximab

Objective To study the biological response of B-cell lymphoma cells to ^131 I-labeled Rituximab, and to investigate the therapeutic effect of ^131 I-Rituximab in lymphoma tumor borne in nude mice,in order to offer experimental evidence for the next radioimmunotherapy. Methods Human B lymphomas cell Raji was cultured in vitro. Raji cell was then inoculated subcutaneously in 30 nude mice. Rituximab was labeled with ^131 I with IODO-GEN method. The cells were randomized into four groups that were ^131 I-Rituximab group, rituximab alone, ^131 I alone and blank group. Its effects on apoptosis and cell cycles of Raji cells were determined by cytometry. Nude mice were randomized into six groups while the tumor was 8 mm in diameter：high,moderate and low dose radioimmunotherapy groups, Rituximab alone,^131 I alone and blank group. The size of the tumor was measured at a 3-day interval and the mice were killed in four weeks after treatment. The tumors were resected and weighed. Results The apoptosis rate measured by Annexin V-FITC/PI was higher than that in other groups. Cell cycle alteration occurred in ^131 I-Rituximab group, and the majority of cells were arrested at G2 stage. As compared to blank group, therapy group had a tumor growth inhibition in a does-and time-dependent manner. The pathological exam proved that the therapy was effective. Conclusion ^131 I-Rituximab can regulate the cycle of Raji cells and induce the apoptosis. The results indicate that the radioimmunological drug made from anti-CD20 monoclonal antibody and ^131 I can specifically localize in tumor tissue and ensure radioimmunological targeting therapy, which has a potential clinical value.