摘要
AIM： To evaluate the multi-step pretargeting radioimmunoimaging （RII） and radioimmunotherapy （RTT） in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153^Sm. METHODS： Two- and three-step strategies for avidinbiotin system pretargeting techniques were established. In a three-step procedure, human colon carcinoma bearing nude mice were first injected with biotinylated monoclonal antibody （McAb-Bt） followed by cold avidin （Av） 48 h later and then 153^Sm-DB2 24 h thereafter; whereas the twostep procedure consisted of injection of 153^Sm-SA 48 h after pretargeting with biotinylated anti-CEA monoclonal antibody （CEA McAb-Bt）. SPECT imaging and biodistribution were performed at 4, 24, 48, or 72 h after injection of 153^Sm-labeled compounds. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 d after grafting. One group received the injection with 100 μg CEA McAb-Bt followed by cold avidin （80 μg） after 2 d and 11.1 MBCl I53Sm-DB2 after 1 d. Four control groups were treated respectively with 11.1 MBq 153^Sm- CEA McAb, ii.i MBq 153^Sm-nmIgG, ii.i MBq 153^Sm-DB2, 100 μL normal saline. Toxicity was evaluated by changes of leukocyte count, and the efficacy by variation in tumor volume. Histological analyses of tumors were performed. RESULTS： The three-step procedure allowed faster blood clearance and yielded higher tumor blood ratios （5.76 at 4 h and 12.94 at 24 h） of the 153^Sm-DB2. The tumor was clearly visualized at 4 h in y-imaging after the injection of 153^Sm-DB2, while a significant accumulation of 153^Sm-SA in the tumor was observed only 24 h after the injection and tumor blood ratios at 4 and 24 h were 1.00 and 2.03, respectively, in the two-step procedure. Pretargeting RIT and 153^Sm-CEA McAb had a strong tumor-inhibiting effect.The tumor inhibitory rate was 80.67% and 78.44%, respectively, five weeks after therapy. Histopathological evidence also indicated radioactive damage in tumor tissues as necrosis of tum
AIM: To evaluate the multi-step pretargeting radioimmunoimaging (RII) and radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153Sm.METHODS: Two- and three-step strategies for avidinbiotin system pretargeting techniques were established.In a three-step procedure, human colon carcinoma bearing nude mice were first injected with biotinylated monoclonal antibody (McAb-Bt) followed by cold avidin (Av) 48 h later and then 153Sm-DB2 24 h thereafter;whereas the twostep procedure consisted of injection of 153Sm-SA 48 h after pretargeting with biotinylated anti-CEA monoclonal antibody (CEA McAb-Bt). SPECT imaging and biodistribution were performed at 4, 24, 48, or 72 h after injection of 153Sm-labeled compounds. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 d after grafting. One group received the injection with 100 μg CEA McAb-Bt followed by cold avidin (80 μg)after 2 d and 11.1 MBq 153Sm-DB2 after 1d. Four control groups were treated respectively with 11.1 MBq 153SmCEA McAb, 11.1 MBq 153Sm-nmIgG, 11.1 MBq 153Sm-DB2,100 Μl normal saline. Toxicity was evaluated by changes of leukocyte count, and the efficacy by variation in tumor volume. Histological analyses of tumors were performed.RESULTS: The three-step procedure allowed faster blood clearance and yielded higher tumor blood ratios (5.76 at4 h and 12.94 at 24 h) of the 153Sm-DB2. The tumor was clearly visualized at 4 h in y-imaging after the injection of 153Sm-DB2, while a significant accumulation of 153Sm-SA in the tumor was observed only 24 h after the injection and tumor blood ratios at 4 and 24 h were 1.00 and 2.03,respectively, in the two-step procedure. Pretargeting RIT and 153Sm-CEA McAb had a strong tumor-inhibiting effect.The tumor inhibitory rate was 80.67% and 78.44%,respectively, five weeks after therapy. Histopathological evidence also indicated radioactive damage in tumor tissues as necrosis of tumor cells, while in the other organs such as liver and kidn
