RECEPTOR BINDING RADIOTRACER FOR SENTINEL NODE IMAGING

用于前哨节点成像的受体结合放射性示踪剂

• 批准号: 2871916
• 负责人: David R. Vera
• 金额: $ 22.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2871916
• 关键词: bioimaging /biomedical imaging; breast neoplasm /cancer diagnosis; breast neoplasms; drug design /synthesis /production; laboratory mouse; laboratory rabbit; lymph nodes; melanoma; metastasis; neoplasm /cancer radiodiagnosis; radiation dosage; radiography; radiopharmacology; radiotracer; receptor binding; swine; technetium

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.

我们建议合成和测试受体结合的放射线药物， [99MTC] DTPA-Mannosyl-Dextran（TCDMD），用于乳房的前哨节点成像 癌症和黑色素瘤。 TCDMD由一个葡聚糖骨干组成 连接甘露糖和DTPA。甘露糖部分与一个受体结合 特定于巨噬细胞的细胞表面。 我们将在以下属性中优化TCDMD的性能：l） 注射部位的快速清除，2）淋巴内高保留率 船只，3）前哨淋巴的快速，完整和持续吸收 节点，4）剩余的区域和远端淋巴结低吸收，5）低 辐射吸收和高生物学安全，6）方便，快速， 和稳定的Technetium-99m标签，具有高放射化学纯度。 [99MTC]锑 - 三硫化物胶体（TCATC）和过滤的胶体不得 展示这些特性。 我们将检验以下假设，即以下五个成像特性 我们提出的哨兵节点成像剂[99mtc] dtpa-mannosyl-dextran是 优于TCATC：l）注射现场清理，2）注射百分比 剂量，3）哨兵节点的峰时间，4）哨兵节点保留 时间和5）吸收目标器官的辐射剂量。这些属性 将在TCDMD和TCATC的前哨节点成像中测量 Sinclair Swine，一种表现出淋巴结的黑色素瘤天然模型 转移。 目前使用的放射性药物不是为 前哨节点成像。我们建议专门针对的代理 哨兵节点的检测应提供明显更高的 放射性药物和成像性能的水平，因此增加 检测效率。总体结果将是更具成本效益的 分期乳腺癌妇女和患者 黑色素瘤。

项目成果

A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran.

用于前哨淋巴结检测的合成大分子：(99m)Tc-DTPA-甘露糖基-葡聚糖。

• 发表时间: 2001
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Vera,DR;Wallace,AM;Hoh,CK;Mattrey,RF
• 通讯作者: Mattrey,RF

Detection of gastric and colonic sentinel nodes through endoscopic administration of 99mTc-DTPA-mannosyl-dextran in pigs.

通过内镜下给予猪 99mTc-DTPA-甘露糖基-葡聚糖来检测胃和结肠前哨淋巴结。

• 发表时间: 2003
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Méndez,Jeanette;Wallace,AnneM;Hoh,CarlK;Vera,DavidR
• 通讯作者: Vera,DavidR