【摘要】 目的用动物血栓栓塞模型显像评估⁹⁹Tc^m 标记人源化抗人血小板膜糖蛋白（GP）Ⅲa单克隆抗体（简称单抗）F（ab）₂片段 SZ21F（ab）₂的应用价值。方法通过体外抑制二磷酸腺苷（ADP）诱导的犬血小板聚集实验,评估 SZ21F（ab）₂与血小板结合的亲和性和特异性。以2-亚氨基噻吩盐酸盐（IT）法修饰 SZ21F（ab）₂分子的亚氨基,以⁹⁹Tc^m-葡庚糖酸钠（GH）转换络合法进行标记。分别用快速薄层层析（ITLC）法和 ELISA 测定标记物的放化纯及生物活性。对3条肺动脉血栓和8条（包括上述3条）后肢深静脉血栓栓塞比格犬模型进行显像研究。结果 SZ21F（ab）₂抑制 ADP 诱导的犬富含血小板血浆（PRP）聚集实验的半数有效剂量(IC₅₀)为（2.49±1.88）μg/ml。ITLC 法测得标记物的放化纯为90%～95%,ELISA 测定结果表明标记后抗体保留了免疫活性。注射显像剂后1 h,肺动脉血栓部位和后肢深静脉血栓部位均出现放射性浓聚。注射后3 h,在体显像肺动脉血栓和后肢深静脉血栓栓塞模型的放射性靶/本底（T/B）比值分别为3.03±1.18和3.51±0.62。肺动脉血栓部位和后肢深静脉血栓部位的每克组织百分注射剂量率（%ID/g）分别为0.083%ID/g 和0.076%ID/g。体外检测结果表明:肺动脉血栓与正常肺组织的单位质量放射性比值平均为12.8,后肢深静脉血栓与血液的单位质量放射性比值平均为5.2,与肌肉的比值平均为127.0。结论 ⁹⁹Tc^m-SZ21F（ab）₂与人血小板具有较高的亲和力,有潜在的血栓显像应用前景。更多还原

【Abstract】 Objective A ⁹⁹Tc^m labeled humanized anti-platelet glycoprotein Ⅲ a monoclonal anti- body F（ab）₂ fragment,with high affinity for human platelet glycoprotein Ⅲa[SZ21 F（ab）₂],was devel- oped for thrombus imaging.Methods The affinity and specificity of SZ21 F（ab）₂ for the GP Ⅲ a receptor was assessed by the inhibition of adenosine diphosphate（ADP）stimulated human platelet aggregation.The primary amines were reacted with 2-iminotholane（IT）to place 7 chelating groups per F（ab）₂ molecule. SZ21 F（ab）₂-IT was labeled by incubation with ⁹⁹Tc^m-glucoheptonate and then tested in vitro before in vivo im- aging of a 24 h-old deep vein thrombosis（DVT）and pulmonary embolism（PE）in a canine model.Results SZ21F（ab）₂ had an IC₅₀of（2.49±1.88）μg/ml in platelet rich plasma,showing high receptor binding affinity and specificity.Focal uptake was observed in planar images as early as 1 h after injection.Lesion uptake of ⁹⁹Tc^m-SZ21F（ab）₂ at 3 h after injection was 0.083 % ID/g for PE and 0.076 % ID/g for DVT. Lesion to background ratios averaged 12.8（PE/lung）,5.2（DVT/blood）,and 127.0（DVT/muscle）. Conclusion ⁹⁹Tc^m-SZ21F（ab）₂ with its modest affinity and high DVT and PE uptake is a promising agent for imaging vascular thrombosis.更多还原