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剂 通过正电子发射断层扫描（PET）来早期检测癌症。 我们将在此阶段进行调查的特定代理人将是一个 针对的互补性区域接枝抗体针对 用锆甲状腺抗原放射性标记。首选 用于蛋白质的锆梯形的双功能螯合物将是 成立。放射性映射，稳定性，体外结合和体内处置 伽马射线发射锆-88-Radiolabel的抗体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，产生和处理正电子的方法论 将开发发射锆-89核素。在阶段结束时 i时期锆89将耦合到最佳抗体形式 证明代理成功成像肿瘤的能力 动物中的异种移植物。具有可行性，在SBIR II期中 工作该方法将扩展到其他人性化的单克隆 抗体。然后至少将其中一个输入I阶段 临床试验以建立人类成像实用程序，如果是 经过证明，该代理将以商业生产规模开发。 最终，用于PET成像的非免疫原性特异性靶向剂 许多癌症被设想。 拟议的商业应用： PET被认为是最敏感的成像方式。单克隆 抗体提供针对定义疾病的特异性以及何时 人性化，本质上是非免疫原性的。通过耦合适当的 带有人源化的单克隆抗体的宠物放射性核素针对 多种癌症，高度，特定和敏感的成像剂 可以尽早发现新的和经常性的癌症。非常 具有重大临床影响和巨大的商业潜力 这样的代理商。