RECEPTOR BINDING RADIOTRACER FOR SENTINEL NODE IMAGING

我们计划合成并测试一种受体结合放射性药物， [99 mTc] DTPA-甘露糖-葡聚糖（TcDMD），用于乳腺前哨淋巴结显像 癌症和黑素瘤。TcDMD由葡聚糖骨架组成， 连接甘露糖和DTPA。甘露糖部分与受体结合， 对巨噬细胞的细胞表面具有特异性。 我们将针对以下特性优化TcDMD的性能： 从注射部位快速清除，2）在淋巴内的高度保留 血管，3）哨兵淋巴快速、完全和持续的摄取 淋巴结，4）剩余区域和远端淋巴结的低摄取，5）低 吸收辐射，生物安全性高; 6）方便、快捷， 和稳定的高放化纯度的锝-99m标记。 [99 mTc]三硫化锑胶体（TcATC）和过滤胶体不 展示这些特性。 我们将测试以下五个成像特性的假设， 我们提出的前哨淋巴结显像剂，[99 mTc] DTPA-甘露糖基-葡聚糖， 上级于TcATC：1）注射部位清除率，2）注射部位清除率 剂量，3）前哨淋巴结达峰时间，4）前哨淋巴结保留 时间; 5）靶器官的吸收辐射剂量。这些属性 将在TcDMD和TcATC的前哨淋巴结成像期间测量， Sinclair猪，一种淋巴结转移的黑色素瘤天然模型 转移 目前使用的放射性药物不是为 前哨淋巴结成像。我们建议，一个专门针对以下方面优化的代理 前哨淋巴结的检测应该提供显著更高的 放射性药物水平和成像性能，因此提高 检测效率总体结果将是更具成本效益的 对患有乳腺癌的妇女和患有乳腺癌的患者进行分期的方法 黑素瘤

We propose to synthesize and test a receptor-binding radiopharmaceutical, [99mTc]DTPA-mannosyl-dextran (TcDMD), for sentinel node imaging of breast cancer and melanoma. TcDMD consists of a dextran backbone to which we attach mannose and DTPA. The mannose moieties bind to a receptor that is specific to the cell surface of macrophages. We will optimize the performance of TcDMD for the following properties: l) rapid clearance from the injection site, 2) high retention within the lymph vessel, 3) rapid, complete, and sustained uptake by the sentinel lymph node, 4) low uptake by remaining regional and distal lymph nodes, 5) low radiation absorption and high biological safety, and 6) convenient, rapid, and stable technetium-99m labeling with high radiochemical purity. [99mTc]Antimony-trisulfide colloid (TcATC) and filtered colloids do not exhibit these properties. We will test the hypothesis that the following five imaging properties of our proposed sentinel node imaging agent, [99mTc]DTPA-mannosyl-dextran, are superior to TcATC: l) injection site clearance, 2) percentage-of-injected dose, 3) time-to-peak in the sentinel node, 4) sentinel node retention time, and 5) absorbed radiation dose of the target organ. These properties will be measured during sentinel node imaging of TcDMD and TcATC in Sinclair swine, a native model of melanoma that exhibits lymph node metastasis. The radiopharmaceuticals currently employed for were not designed for sentinel node imaging. We propose that an agent optimized specifically for the detection of the sentinel node should provide a significantly higher level of radiopharmaceutical and imaging performance and therefore increase detection efficiency. The overall result will be a more cost effective procedure for staging women with breast cancer and patients suffering from melanoma.