放射免疫结合外照射对实体瘤的实验研究

目的 探讨放射免疫结合外照射对实体瘤的外照射剂量、二者最佳的应用时机与顺序。方法 TS1是一种抗细胞角蛋白8的单克隆抗体，它可以与肿瘤坏死区域中的细胞角蛋白(CKs)8特异地结合，用^131I标记单克隆抗体形成放射性螫合物。60只荷瘤(人宫颈鳞癌)小鼠用于研究：24只做预实验，观察肿瘤的退缩情况，决定合适的外照射剂量；36只做正式实验，分为6个组，分别给不同的治疗方案后比较肿瘤中放射活度比、平均累积吸收剂量、累积吸收总量以及全身放射性螯合物药代动力学。结果 预实验中，当肿瘤接受20Gy外照射时生长明显受抑，增加剂量肿瘤受抑幅度减小。正式实验中，给药前进行外照射组，肿瘤放射活度比、平均累积吸收剂量、累积吸收总量最高，与其他组相比有显著性差异。结论 ^131I-TS1放射免疫导向结合外照射治疗实体瘤，在给药前行20Gy的外照射组中，肿瘤放射活度比、平均累积吸收剂量、累积吸收总量最高，疗效最佳。

Combined radioimmunotherapy and external irradiation for solid tumors in the mouse

Objective To evaluate the optimal external irradiation dose and potential benefits with different treatment timing strategies and sequence of combined external irradiation and radioimmunotherapy for solid tumors in the mouse.Methods TS1, a monoclonal antibody directed against anticytokeratin 8, can specifically combined with anticytokeratin in the necrotic parts of tumors. Mab TS1 was iodinated with 131 I. Among sixty nude mice with tumor cells xenografts(human cervical squamous carcinoma) used in this study, twenty-four were used in a pilot experiment to determine the appropriate level of external irradiation dose by observing the tumor growth inhibition while thirty-six were used in the experiment proper which were divided into 6 groups and given different treatment protocols. Total accumulated dose, percentage of injected activity per gram of tumor tissue and accumulated dose per injected activity were compared between these different groups. Results In the pilot experiment, the tumor growth was inhibited markedly by 20 ?Gy of external irradiation, but the response did not significantly increase when the dose was increased to 26 ?Gy. In the experiment proper, the highest yields in terms of total accumulated dose, percentage of injected activity per gram of tumor tissue and accumulated dose per injected activity were seen in the group which received external irradiation prior to Mab injection. Conclusions Enhanced effects can be achieved by combined external irradiation with radioimmunotherapy using the monoclonal anticytokeratin antibody 131 I -TS1. 20 ?Gy of external irradiation should be given prior to Mab injection.