BIFUNCTIONAL CHELATES IN CANCER IMAGING AND THERAPY

双功能螯合物在癌症成像和治疗中的应用

• 批准号: 3168090
• 负责人: DAVID A GOODWIN
• 金额: $ 13.23万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168090
• 关键词: amines; autoradiography; bleomycin; brain neoplasms; carcinoembryonal antigen; cell membrane; chelating agents; chromium; cobalt; drug metabolism; electron microscopy; ethylenediaminetetraacetate; human subject; human therapy evaluation; image processing; immunoglobulin G; isomer; ligands; membrane permeability; metastasis; neoplasm /cancer immunology; neoplasm /cancer pharmacology; neoplasm /cancer radionuclide diagnosis; neoplasm /cancer radionuclide therapy; radiotracer; technetium; transferrin

We will investigate the biological properties of molecules labeled using bifunctional chelates with the aim of developing clinically useful tumor localizing agents. We will study two new derivatives of bleomycin, BLEDTA II and BLEDTA III, as well as the protein chelate conjugates of transferrin and monoclonal antibodies. Radiotracer kinetics and electron microscope autoradiography will be used to study the binding to putative receptors on the tumor cell surface, the mechanisms of transport into the cell cytosol and the metabolism by the cell. We will use chemical, radiochemical, enzymatic and immunologic strategies to maximize tumor concentration while lowering the blood background using a tumor mouse model of BALB/c mice bearing KHJJ tumor. We will test in vitro and in vivo tumoricidal properties of the best "carriers", containing Auger or alpha particle emitters, redox groups, photoreactive groups or covalently bound antitumor drugs. The best tumor imaging agents will be selected for the study of dosimetry, sensitivity and specificity of cancer localization in cancer patients.

我们将研究使用使用的分子的生物学特性 双功能螯合物的目的是开发临床上有用的肿瘤 本地化代理。 我们将研究博来霉素的两个新衍生物Bledta II和BLEDTA III，以及转铁蛋白的蛋白质螯合物 和单克隆抗体。 放射性练习动力学和电子显微镜 放射自显影将用于研究与推定受体的结合 肿瘤细胞表面，转运到细胞胞质的机制 和细胞的新陈代谢。 我们将使用化学，放射化学， 酶和免疫学策略以最大化肿瘤浓度 使用BALB/C小鼠的肿瘤小鼠模型降低血液背景 带有KHJJ肿瘤。 我们将在体外和体内肿瘤测试 最佳“载体”的特性，包含螺旋钻或α粒子 发射器，氧化还原组，光电反应组或共价结合的抗肿瘤 毒品。 将选择最好的肿瘤成像剂进行研究 癌症中癌症定位的剂量，敏感性和特异性 患者。