摘要
Objective To evaluate the usefulness of 99m Tc labelled chimeric mouse/human monoclonal antibody (McAb) SZ 51 Hu for detection of vascular thrombi. Methods The mouse/human chimeric McAb SZ 51 Hu against activated platelets was produced and labelled with 99m Tc using 2 iminothiolane modification McAb and 99m Tc glucoheptonate (GH) transchelation method. The canine experimental models of femoral arterial thrombosis were prepared through injecting with 99m Tc SZ 51 Hu intravenously and then imaged by SPECT. 99m Tc labelled murine McAb SZ 51 was used as a positive control. Results The arterial thrombi were clearly discernible at 2 to 4h after injection of 99m Tc SZ 51 Hu. Radiolabelled antibody was cleared from the blood with T 1/2α of 0.37±0.24 h and T 1/2β of 8.23±3.70 h for SZ 51 Hu, T 1/2α of 0.60±0.17 h and T 1/2β of 9.17±4.44 h for SZ 51, respectively. Quantitative analysis showed that the ratios between the thrombus and the opposite vessel were increased strikingly over time. The ratios of thrombus to blood or surrounding muscle were 33.05±7.78 and 210.68±192.97 for SZ 51 Hu, 36.33±5.30 and 234.02±76.91 for SZ 51 after sacrifice. No differences were observed between SZ 51 Hu and SZ 51 in binding, blood clearnce and biodistribution (P>0.05). Conclusions 99m Tc SZ 51 Hu retained the binding specificity of the parent murine McAb. Therefore, the mouse/human chimeric monoclonal antibody SZ 51 Hu may be a potential agent for diagnosis and therapy o thrombotic disease. The value of this McAb in human patients and its immunogenicity need to be evaluated in clinical trials.
Objective To evaluate the usefulness of 99m Tc labelled chimeric mouse/human monoclonal antibody (McAb) SZ 51 Hu for detection of vascular thrombi. Methods The mouse/human chimeric McAb SZ 51 Hu against activated platelets was produced and labelled with 99m Tc using 2 iminothiolane modification McAb and 99m Tc glucoheptonate (GH) transchelation method. The canine experimental models of femoral arterial thrombosis were prepared through injecting with 99m Tc SZ 51 Hu intravenously and then imaged by SPECT. 99m Tc labelled murine McAb SZ 51 was used as a positive control. Results The arterial thrombi were clearly discernible at 2 to 4h after injection of 99m Tc SZ 51 Hu. Radiolabelled antibody was cleared from the blood with T 1/2α of 0.37±0.24 h and T 1/2β of 8.23±3.70 h for SZ 51 Hu, T 1/2α of 0.60±0.17 h and T 1/2β of 9.17±4.44 h for SZ 51, respectively. Quantitative analysis showed that the ratios between the thrombus and the opposite vessel were increased strikingly over time. The ratios of thrombus to blood or surrounding muscle were 33.05±7.78 and 210.68±192.97 for SZ 51 Hu, 36.33±5.30 and 234.02±76.91 for SZ 51 after sacrifice. No differences were observed between SZ 51 Hu and SZ 51 in binding, blood clearnce and biodistribution (P>0.05). Conclusions 99m Tc SZ 51 Hu retained the binding specificity of the parent murine McAb. Therefore, the mouse/human chimeric monoclonal antibody SZ 51 Hu may be a potential agent for diagnosis and therapy o thrombotic disease. The value of this McAb in human patients and its immunogenicity need to be evaluated in clinical trials.
