Radioimmunoscintigraphy of experimental arterial thrombi in dogs with 99mTc labelled chimeric monoclonal antibody against human activated platelets SZ-51Hu

PURPOSE: To evaluate the usefulness of 99mTc labelled chimeric mouse/human monoclonal antibody (McAb) SZ51Hu for detection of vascular thrombi. METHODS: The mouse/human chimeric McAb SZ-51Hu against activated platelets was produced and labelled with 99mTc using 2-iminothiolase modification McAb and 99mTc-glucoheptonate (GH) transchelation method. The canine experimental models of femoral arterial thrombosis were prepared through injecting with 99mTc-SZ-51Hu intravenously and then imaged by SPECT. 99mTc-labelled murine McAb SZ-51 was used as a positive control. RESULTS: The arterial thrombi were clearly discernible at 2 to 4 h after injection of 99mTc-SZ-51Hu. Radiolabelled antibody was cleared from the blood with T1/2α of 0.37 +- 0.24 h and T1/2β of 8.23 +-3.70 h for SZ-51Hu, T1/2α of 0.60 +- 0.17 h and T1/2β 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-51Hu, 36.33 +- 5.30 and 234.02 +- 76.91 for SZ-51 after sacrifice. No differences were observed between SZ-51Hu and SZ-51 in binding, blood clearance and biodistribution (P>0.05). CONCLUSIONS: 99mTc-SZ-51Hu retained the binding specificity of the parent murine McAb. Therefore, the mouse/human chimeric monoclonal antibody SZ-51Hu may be a potential agent for diagnosis and therapy of thrombotic disease. The value of this McAb in human patients and its immunogenicity need to be evaluated in clinical trials