IMAGING OF DVT AND PE WITH TC-99M-BITISTATIN

目前迫切需要一种快速定位肺栓塞的方法 (PE)以及潜在的进一步栓塞的来源，深静脉 血栓（DVT）。 9 kD肽bitistatin以高亲和力结合至 活化血小板上的糖蛋白IIb/IIIa受体。 当 用123 I放射性标记的比替他汀已被发现对 动物模型中实验性PE和DVT的快速成像。 的 本项目的总体目标是开发Tc-99 m标记的比替他汀， 用于PE和DVT成像的放射性药物。 首先，bitistatin将 使用HYNIC螯合剂用Tc-99 m进行放射性标记。 行为 Tc-99 m-bitistatin与I-125-bitistatin在体外进行比较， 与血小板结合（未刺激和刺激）。稳定性 标签也将被研究。 第二，Tc-99 m的能力- 然后将在动物中评价bitistatin对DVT和PE的成像 模型 Tc-99 m标记的图像质量和组织分布 将测定bitistatin并与碘化bitistatin进行比较。 未来的研究将执行安全性，开发大规模的方法， 在临床试验之前进行生产和测试 疑似血栓栓塞性疾病的患者。 这 放射性药物具有快速、直接和有效的临床应用潜力。 DVT和PE的成像。 一个单一的诊断成像测试， 对这两种类型病变进行成像将有助于初步诊断， 以及用于监测治疗效果。 建议的商业应用 一个单一的诊断测试，可以成像DVT和PE将是 对于初步诊断以及监测 疗法

There is an urgent need for a method to rapidly locate pulmonary emboli (PE) as well as the source of potential further emboli, deep venous thrombi (DVT). The 9kD peptide bitistatin binds with high affinity to the glycoprotein IIb/IIIa receptor on activated platelets. When radiolabeled with 123I, bitistatin has been found to have efficacy for rapid imaging of experimental PE and DVT in an animal model. The overall goal of this project is to develop Tc-99m labeled bitistatin as a radiopharmaceutical for imaging PE and DVT. First, bitistatin will be radiolabeled with Tc-99m using HYNIC chelating agent. The behavior of Tc-99m-bitistatin will be compared with I-125-bitistatin in vitro for binding to platelets (both nonstimulated and stimulated). Stability of the label will also be studied. Second, the ability of Tc-99m- bitistatin to image DVT and PE will then be evaluated in an animal model. Image quality and tissue distribution of the Tc-99m labeled bitistatin will be determined and compared with iodinated bitistatin. Future studies will perform the safety, develop a method for large-scale production and perform testing needed prior to a clinical trial in patients with suspected thromboembolic disease. This radiopharmaceutical has potential clinical utility for rapid, direct imaging of DVT and PE. A single diagnostic imaging test which could image both types of lesions would be useful for initial diagnosis as well as for monitoring the effects of therapy. PROPOSED COMMERCIAL APPLICATION A single diagnostic test which could image both DVT and PE would be valuable for initial diagnosis as well as for monitoring the effects of therapy.