PRACTICAL RE 186 LABELED PRODUCTS FOR RADIOIMMUNOTHERAPY

用于放射免疫治疗的实用 RE 186 标记产品

• 批准号: 2106243
• 负责人: SERENGULAM V GOVINDAN
• 金额: $ 8.1万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2106243
• 关键词: antibody specificity; antitumor antibody; athymic mouse; carcinoembryonal antigen; chelating agents; chemical synthesis; disease /disorder model; drug design /synthesis /production; immunoconjugates; immunoglobulin G; lyophilization; monoclonal antibody; neoplasm /cancer pharmacology; neoplastic cell; pharmacokinetics; radionuclides; radiotracer

The ultimate goal of this project is to develop a readily usable rhenium- 186-labeled monoclonal antibody product for radioimmunotherapy of colorectal and other types of cancer. Rhenium-186 (t1/2=90h) has beta- emissions at 1.07 meV and 0.93 MeV, and imageable gamma-emission (9% abundance) at 137 KeV. The Phase-I research will involve preparation of chelator-linked conjugates of a high-affinity CEA-specific antibody, single-vial formulations of the same with tin, and demonstration of expeditious and sit-specific labeling with rhenium-186 perrhenate. Biodistributions of these radioimmunoconjugates in tumor-bearing mice will be determined. The objective is to produce a lyophilized antibody preparation which can be labeled, in one step, to obtain a radioimmunoconjugate with high immunoreactivity, and an in vivo retention resembling that of iodinated antibody. a product fulfilling these criteria will be easily usable in hospital settings, and commercially viable. Initial labeling experiments will be carried out using rhenium- 188 perrhenate, which is readily available from an in-house tungsten- rhenium generator. Extensive animal preclinical studies, and initial clinical studies will be carried out in an SBIR Phase II program.

该项目的最终目标是开发一种易于使用的Re- 用于放射免疫治疗的186标记单抗产品 结直肠癌和其他类型的癌症。~(186)Re(t1/2=90h)具有β- 1.07 MeV和0.93 MeV的辐射，以及可成像的伽马辐射(9% 丰度)在137keV。第一阶段的研究将包括准备 高亲和力CEA特异性抗体的螯合剂连接的结合物， 与锡的单瓶配方，并演示了 Re-186Perrhenate快速和Site特异性标记。 这些放射免疫结合物在荷瘤小鼠体内的生物分布 将会被确定。目的是生产一种冻干抗体 可在一步中标记以获得一种 具有高免疫反应性和体内保留的放射免疫结合物 与碘化抗体相似。一种满足这些要求的产品 标准将很容易在医院环境中使用，并在商业上使用 可行。初步的标记实验将使用Re- 188高锰酸盐，它可以从内部的钨- Re发生器。广泛的动物临床前研究，以及初步的 临床研究将在SBIR第二阶段计划中进行。