Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, China 188 Shizi Street, Suzhou, Jiangsu, China, 215006.
Thromb Res. 2012 Nov;130(5):703-8. doi: 10.1016/j.thromres.2012.07.028. Epub 2012 Sep 8.
Rapid and timely diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) is important to improve patient outcome. The goal of this study was using (99m)Tc-chSZ21-F(ab)(2), F(ab)(2) fragment of anti-glycoprotein IIIa chimeric monoclonal antibody, to image experimental thromboembolism (DVT and PE) in dogs.
Flow cytometry assay and adenosine diphosphate (ADP) stimulated platelet aggregation was performed to determine the specificity and affinity of chSZ21-F(ab)(2) to the GPIIb/IIIa receptor on human or canine platelets. Both PE and DVT were induced in 12 beagle canines by catheter under X-ray direction. After (99m)Tc-chSZ21-F(ab)(2) injection,animals were imaged for up to 3 hours then heparinized and sacrificed.
Specific binding of chSZ21-F (ab)(2) to GPIIb/IIIa on human or canine platelets was verified by flow cytometry assay. chSZ21-F (ab)(2) inhibited ADP induced platelet aggregation with a dose-dependent manner, the concentration required to inhibit 50% (IC(50)) of platelet aggregation was 11.6 ± 7.9 nM and 24.9 ± 18.8 nM for human and canine, respectively. In vivo, focal uptake was observed in planar images as early as 30 min (DVT) and 60 min (PE), and became clearer within 3 hours after injection. Lesion-to-background ratio averaged 12.8 (PE-to-lung), 7.2 (DVT-to-blood), and 117.0(DVT-to-muscle), respectively.
These results suggested that (99m)Tc-chSZ21-F(ab)(2) with high DVT and PE uptake is a promising agent for imaging vascular thrombosis.
快速及时地诊断肺栓塞（PE）和深静脉血栓形成（DVT）对于改善患者预后非常重要。本研究的目的是使用（99m）Tc-chSZ21-F（ab）（2），即抗糖蛋白 IIIa 嵌合单克隆抗体的 F（ab）（2）片段，对实验性血栓栓塞（DVT 和 PE）进行成像。
通过流式细胞术测定和二磷酸腺苷（ADP）刺激的血小板聚集，确定 chSZ21-F（ab）（2）与人类或犬血小板上的 GPIIb/IIIa 受体的特异性和亲和力。通过 X 射线引导的导管，在 12 只比格犬中诱导 PE 和 DVT。（99m）Tc-chSZ21-F（ab）（2）注射后，动物在 3 小时内进行成像，然后用肝素化并处死。
通过流式细胞术测定，证实了 chSZ21-F（ab）（2）与人类或犬血小板上的 GPIIb/IIIa 的特异性结合。chSZ21-F（ab）（2）以剂量依赖性方式抑制 ADP 诱导的血小板聚集，抑制 50%血小板聚集所需的浓度（IC（50））对于人类和犬分别为 11.6±7.9 nM 和 24.9±18.8 nM。在体内，30 分钟（DVT）和 60 分钟（PE）时即可在平面图像中观察到局灶性摄取，注射后 3 小时内变得更清晰。病变与背景的比值平均为 12.8（PE-肺）、7.2（DVT-血液）和 117.0（DVT-肌肉）。
这些结果表明，（99m）Tc-chSZ21-F（ab）（2）具有高 DVT 和 PE 摄取，是一种有前途的血管血栓成像剂。
