摘要
目的 探讨1 5 3Sm标记亲和素 生物素系统 (ABS)在荷人结肠癌裸鼠模型中进行抗CEA单克隆抗体 (McAb)预定位放免显像的可行性。方法 首先用1 5 3Sm标记螯合DTPA生物素 (DB2 ) ,然后利用生物素与亲和素 (AV)的高亲和力特性 ,对链霉亲和素 (SA)进行1 5 3 Sm标记 ,通过DTPA环酐法将1 5 3Sm标记到抗CEAMcAb上。应用三步法方法A(生物素化CEAMcAb AV 1 5 3 Sm标记DB2 )和方法B(链霉亲和素化CEAMcAb 生物素 1 5 3Sm标记SA)以及二步法方法A(生物素化CEAMcAb 1 5 3Sm标记SA)和方法B(链霉亲和素化CEAMcAb 1 5 3Sm标记DB2 )预定位于荷人结肠癌裸鼠 ,分别于注射放射性标记物后 4～ 72h进行γ显像和体内分布测定。以1 5 3 Sm CEAMcAb、1 5 3Sm SA、1 5 3Sm DB2 和生物素化正常鼠IgG AV 1 5 3 Sm标记DB2 作为对照组。结果 三步法 :方法A在标记物引入后 4h肿瘤即显影 ,其肿瘤 %ID g在 4和 2 4h分别为 1 78和 1 36 ,而血T NT分别为 5 76和 12 94,血T NT均显著高于各对照组 ;方法B肿瘤部位未见明显放射性摄取 ,其肿瘤 %ID g和血T NT与1 5 3 Sm SA对照组相近。二步法 :方法A在标记物引入 2 4h肿瘤即有放射性聚集 ,血T NT为 2 0 3,肿瘤的 %ID g为 2 10 ,且随预定位时间增加未见明显降低 ;
Objective To evaluate the usefulness of 153 Sm labelled avidin biotin system in pretargeting radioimmunoimaging (RII)with anti CEA McAb Methods Chelate DTPA biotin (DB 2) was first radiolabeled with 153 Sm and then bound this 153 Sm DB 2 to streptavidin (SA) The labeling of McAb with 153 Sm was conducted using the bifunctional chelate cyclic DTPA anhydride (cDTPAa) Experimental studies were carried out in nude mice bearing human colon carcinoma We established two and three step strategies for avidin biotin system pretargeting techniques In three step method A, tumor bearing nude mice were first injected with McAb biotin followed by cold avidin (Av) 2 days later and then 153 Sm DB 2 1 day after But in three step method B, one group of mice was injected with McAb SA followed by cold biotin 2 days later, and 4 h after biotin, by 153 Sm SA While two step protocols consisted of the injection of 153 Sm SA 48 h or 96 h after pretargeting with McAb bition (method A); and the injection of 153 Sm DB 2 48 h after the use of McAb SA (method B) SPECT imaging was performed and biodistribution was studied at 4, 24, 48 or 72 h after injection of 153 Sm labeled compounds Results Our results showed that: ①The three step method A allowed faster blood clearance of the 153 Sm DB 2 and yielded higher T/NT ratios (5 76 at 4 h and 12 94 at 24 h) ②In the two step method A, a significant accumulation of 153 Sm SA was observed in the tumor of nude mice which were injected 153 Sm SA 2 days after pretargeting The uptake in the tumor was also relatively high even in nude mice received 153 Sm SA 4 days after pretargeting, demonstrating that the McAb bition was still bound to the tumors and accessible to the 153 Sm SA even after long period of time ③Two and three step method A could increase the T/NT ratio in RII, shortening the imaging time (24 and 4 h, respectively) Conclusions Aforementioned studies provide an experimental evidence for the improvement of pretargeting technique and the further clinical application of pretargeting RII and radioimmunotherapy
出处
《中华核医学杂志》
CSCD
北大核心
2000年第3期120-123,共4页
Chinese Journal of Nuclear Medicine
关键词
ABS
单克隆抗本
放射免疫测定
结肠肿瘤
Avidin biotin system
Antibodies
monoclonal
Carcinoembryonic antigen
Radioimmunodetection
Colonic neoplasms
