亲和素-生物素系统预定位放免治疗的实验研究

摘要

选用153Sm标记抗CEA单抗(McAb)和螯合DTPA生物素(DB2),利用生物素化单抗-亲和素-153Sm-DB2的三步法在荷人结肠癌裸鼠模型中进行预定位放免治疗。以153Sm-CEA McAb、153Sm-mIgG、153Sm-DB2作为治疗对照组,100μL 生理盐水作为非治疗对照组,在移植瘤接种后的第3天实施治疗,采用单次较大剂量治疗(11.1MBq/每鼠),定期测量裸鼠的体重、血白细胞计数和肿瘤生长体积以及瘤块的组织病理学检查,观察肿瘤抑制效应及毒副作用。结果表明,预定位放免治疗与直接标记单抗放免治疗对肿瘤有明显的抑制作用,治疗第5周肿瘤抑制率分别达到80.67%和78.44%,组织病理学结果提示肿瘤组织呈坏死样改变,而正常脏器如肝、肾等未见损伤;治疗前后白细胞计数以153Sm-CEA McAb及153Sm-mIgG两组降低最为显著。提示预定位放免治疗具有低毒高效的治疗作用,较153Sm-CEA McAb具有更大的安全性。%The aim of this work is to compare the toxicity and efficacy of three-step pretargeting radioimmunotherapy involving administration of a biotinylated anti-carcinoembryonic antigen (CEA) antibody, followed by avidin followed finally by 153Sm labelled biotin with 153Sm directly labelled anti-CEA monoclonal antibody(McAb). CEA McAb and DTPA-biocytin (DB2) was labelled with 153Sm using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 days after the graft. One group received the injection of 100μg McAb-Bt followed 2 days later by cold Av (80μg)and 11.1MBq 153Sm-DB2 after a further day. Four control groups were treated respectively with (1) 11.1MBq 153Sm-CEA McAb, (2) 11.1MBq 153Sm-mIgG, (3) 11.1MBq 153Sm-DB2, (4) 100μL physiological sodium chloride solution. Toxicity was evaluated by change of body weight and number of leukocytes, and efficacy was evaluated by variation in tumor volume. Histological analysis of tumors were performed. The results showed that pretargeting RIT and 153Sm-CEA McAb had a strong tumor inhibition effect. The inhibitory rates of tumor were 80.67% and 78.44% respectively, five weeks after therapy. Histopathological evidence indicated that in tumor tissues radioactive damage was seen as necrosis of tumor cells， while in the other tissues such as liver and kindey tissues no radioactive damage was observed. Leukocyte counts were singnificantly decreased after treatment in groups of 153Sm-CEA McAb and 153Sm-mIgG， which indicated that the haemopoitic function of bone marrow may be affected. It was concluded that three-step pretargeting radioimmunotherapy was as efficient as 153Sm-CEA McAb but was markedly less toxic.