PRE-TARGETED GALLIUM-68 POSITRON EMISSION TOMOGRAPHY

预靶向镓 68 正电子发射断层扫描

• 批准号: 6015611
• 负责人: GARY Leonard GRIFFITHS
• 金额: $ 10万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-16 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6015611
• 关键词: antibody specificity; athymic mouse; bioimaging /biomedical imaging; carcinoembryonal antigen; diagnosis design /evaluation; gallium; immunoglobulin structure; iodine; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer radionuclide diagnosis; positron emission tomography; radiotracer; tumor antigens

The aim of this work is to determine the feasibility of using Ga-68 for positron emission tomography by specifically tumor-targeting the nuclide, using bispecific antibody fragments having one arm reactive with tumor antigen and a second arm reactive with a Ga-68 low molecular weight hapten. We will iodine-l25 label an anti-carcinoembryonic antigen complementarity determining region-grafted x murine antidiethylenetriaminepentaacatec acid bispecific F(ab')2 fragment. We will Ga-68 radiolabel a low molecular weight peptide substituted with two diethylenetriaminepentaacatec acid molecules. The agents will be tested in in vitro binding studies to determine binding to each other and tumor antigen. Affinities of the components will be determined. The pretargeting system will be evaluated in vivo using human tumorxenograft models in athymic nude mice and I-l25/Ga-68 dual radiolabeled components. At the end of the Phase I period we aim to have established a method that gives strongly positive tumor-to-all normal organ ratios. Ultimately, we will the combine the strengths of tumor-specific antibody targeting with the sensitivity of positron emission tomography, and with the practical convenience of the gallium-68 generator. PROPOSED COMMERCIAL APPLICATIONS: A generally usable system for highly disease-specific and sensitive imaging of cancer would change the paradigm of how the disease is detected and monitored. The specific agents and method we intend to develop under this SBIR, represents an example of such a system. The specific agents of this SBIR are for colon cancer detection, and would have high commercial, potential in this common disease in westernized countries.

这项工作的目的是确定使用GA-68用于正电子发射断层扫描的可行性，该可行性使用双臂抗体片段特异性地靶向核素，该抗体片段具有一个用肿瘤抗原反应的手臂，并用GA-68低分子反应型。体重触觉。我们将碘-L25标记抗​​肉眼胚抗原互补性，以确定区域接枝的X鼠抗二乙基苯基苯甲酸盐酸双特异性双特异性F（AB'）2片段。我们将GA-68放射性标记用两个二乙基三位体苯甲酸分子取代的低分子量肽。将在体外结合研究中测试这些药物，以确定彼此结合和肿瘤抗原。将确定组件的亲和力。预先定位的系统将在无胸腺裸鼠和I-L25/GA-68双重放射性标记的成分中使用人类肿瘤移植模型在体内进行评估。在第一阶段结束时，我们的目标是建立一种可以给出强烈肿瘤的正常器官比率的方法。最终，我们将靶向肿瘤特异性抗体的强度与正电子发射断层扫描的敏感性以及镀锌-68发电机的实际便利性结合在一起。拟议的商业应用：通常可用于高度疾病的癌症成像的系统，将改变检测和监测疾病的范例。我们打算在此SBIR下开发的特定代理和方法代表了这种系统的一个示例。该SBIR的特定药物用于结肠癌检测，在西方国家的这种常见疾病中具有很高的商业潜力。