Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab′ fragment (99mTc-DI-DD3B6/22-80B3): results of a phase I trial
Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab′ fragment (99mTc-DI-DD3B6/22-80B3): results of a phase I trial
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DOI：
10.1007/s00259-008-0934-7
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发表时间：
2009-02-01
影响因子：
9.1
通讯作者：
Scott, Andrew M.
中科院分区：
文献类型：
--
作者：
Macfarlane, David;Socrates, Angelides;Scott, Andrew M.
目的Tc99m-DI-DD3B6/22-80B3(ThromboView(R)，以下简称Tc99m-DI-80B3Fab‘)是一种放射性标记的人源单抗Fab’片段，具有亲和力和对交联型纤维蛋白D-二聚体的特异性。在犬类模型中已经证实了血栓栓塞症的检测。研究目的是评价99m-DI-80B3Fab‘在急性下肢深静脉血栓患者体内的生物分布、免疫原性和药代动力学特征及其安全性。其中21例单次静脉注射0.5 mg(n=6)、1.0 mg(n=9)或2 mg(n=6)~(99m)Tc-DI-80B3Fab‘。给药后24小时采集血样、尿样和伽马摄像图像，进行药代动力学和剂量学分析。在给药后30天内监测生命体征、心电图、血液学和生化数据以及人类抗人抗体(HAHA)水平。结果21例受试者中有15例发生了35例不良反应。认为可能与服用Tc99m-DI-80B3Fab‘有关的患者包括轻度高血压、轻度乳酸脱氢酶升高和中度丙氨酸转氨酶升高。哈哈检测仍然是阴性的。药代动力学和器官剂量测定与之前的正常志愿者数据相似。血栓视图(R)在注射后30分钟就已明显定位于已知血栓的部位。结论在急性DVT患者中，Tc99m-DI-80B3Fab‘耐受性良好，具有检测急性静脉血栓形成的有利特征。
Purpose Tc-99m-DI-DD3B6/22-80B3 (ThromboView (R), hereafter abbreviated to Tc-99m-DI-80B3 Fab') is a radio-labelled humanised monoclonal Fab' fragment with affinity and specificity for D-dimer domains of cross-linked fibrin. Detection of thromboembolic events has been demonstrated in canine models. The study objectives were evaluation of safety and characterisation of biodistribution, immunogenicity and pharmacokinetic profile of increasing doses of Tc-99m-DI-80B3 Fab' in subjects with acute lower-limb DVT.Methods Twenty-six patients with acute lower limb DVT were enrolled. Of these, 21 received a single intravenous dose of 0.5 mg (n=6), 1.0 mg (n=9) or 2 mg (n=6) Tc-99m-DI-80B3 Fab'. Blood and urine samples and gamma camera images were collected to 24 h after administration for pharmacokinetic and dosimetry analysis. Vital signs, electrocardiography, hematological and biochemical data and human anti-human antibody (HAHA) levels were monitored for up to 30 days following administration. Patients were assigned to either planar or single photon emission computed tomographic (SPECT) imaging of the thorax at 4 h following injection.Results Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of Tc-99m-DI-80B3 Fab' included mild hypertension, mild elevation of LD ( lactate dehydrogenase) and moderate elevation of ALT ( alanine transaminase). HAHA assays remained negative. Pharmacokinetics and organ dosimetry were comparable to prior normal volunteer data. Localisation of Thromboview (R) to sites of known thrombus was evident as early as 30 min post-injection.Conclusions In subjects with acute DVT, Tc-99m-DI-80B3 Fab' was well tolerated with favourable characteristics for the detection of acute venous thrombosis.