POSITRON EMISSION TOMOGRAPHY WITH MONOCLONAL ANTIBODIES

使用单克隆抗体进行正电子发射断层扫描

• 批准号: 2535884
• 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: 1998
• 资助国家: 美国
• 起止时间: 1998-09-24 至 1999-03-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2535884
• 关键词: carcinoembryonal antigen; contrast media; immunoglobulin G; immunoglobulin structure; laboratory mouse; monoclonal antibody; pharmacokinetics; positron emission tomography; radiotracer; zirconium

The aim of this work is to produce monoclonal antibody-based agents for use in early detection of cancer by positron emission tomography (PET). The specific agent we will investigate in this phase I work will be a complementarity-determining region-grafted antibody targeted against carcinoembryonic antigen radiolabeled with zirconium. The preferred bifunctional chelate for zirconium radiolabeling of proteins will be found. Radiolabeling, stability, in vitro binding and in vivo disposition of gamma-ray-emitting zirconium-88-radiolabeled antibody IgG, F(ab')2 and Fab' moieties will be studied to determine the probable optimal antibody form. In parallel, methodologies to produce and process the positron- emitting zirconium-89 nuclide will be developed. At the end of the phase I period the zirconium-89 will be coupled to the optimal antibody form to demonstrate the ability of the agent to successfully image tumor xenografts in animals. With feasibility demonstrated, in SBIR phase II work the method will be extended to other humanized monoclonal antibodies. At least one of these will then be entered into phase I clinical trials to establish human imaging utility and, if that is proven, the agent will be developed on a commercial production scale. Ultimately, non-immunogenic specific targeting agents for PET imaging of many cancers are envisioned. PROPOSED COMMERCIAL APPLICATIONS: PET is considered to be a most sensitive imaging modality. Monoclonal antibodies offer targeting specificity to defined diseases and when humanized, are essentially non-immunogenic. By coupling an appropriate PET radionuclide with humanized monoclonal antibodies directed against diverse cancers, highly, specific and sensitive imaging agents for the early detection of new and recurrent cancers would become available. Very significant clinical impact and great commercial potential exists for such agents.

这项工作的目的是生产基于单克隆抗体的药物 正电子发射断层扫描（PET）用于早期癌症检测。 我们在本阶段工作中将调查的具体代理将是 互补决定区嫁接抗体靶向 用锆放射性标记的癌胚抗原。首选 用于蛋白质的锆放射性标记的双功能螯合物将是 成立。放射性标记、稳定性、体外结合和体内处置 伽马射线发射锆 88 放射性标记抗体 IgG、F(ab')2 和 将研究 Fab' 部分以确定可能的最佳抗体 形式。同时，生产和处理正电子的方法 开发发射锆89核素。阶段结束时 我期锆89将与最佳抗体形式偶联 证明试剂成功成像肿瘤的能力 动物异种移植。 SBIR 第二阶段已证实可行性 该方法将扩展到其他人源化单克隆抗体 抗体。至少其中一个将进入第一阶段 建立人体成像实用性的临床试验，如果是的话 经证实，该制剂将在商业生产规模上进行开发。 最终，用于 PET 成像的非免疫原性特异性靶向剂 预计会出现许多癌症。 拟议的商业应用： PET 被认为是最灵敏的成像方式。单克隆 抗体提供针对特定疾病的靶向特异性，以及何时 人源化，基本上是非免疫原性的。通过耦合适当的 PET放射性核素与人源化单克隆抗体针对 多种癌症，高度、特异性和灵敏的显像剂 新发癌症和复发癌症的早期检测将成为可能。非常 存在重大的临床影响和巨大的商业潜力 这样的代理。