PRACTICAL RE 186 LABELED PRODUCTS FOR RADIOIMMUNOTHERAPY

用于放射免疫治疗的实用 RE 186 标记产品

基本信息

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
项目类别：
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

项目摘要

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.

该项目的最终目的是开发一个易于使用的rhenium- 186个标记的单克隆抗体产品，用于放射免疫疗法结直肠癌和其他类型的癌症。 Rhenium-186（T1/2 = 90H）具有β- 1.07 MEV和0.93 MEV的排放量和可成像的伽马排放（9％丰度）在137 Kev。 I期研究将涉及准备高亲和力CEA特异性抗体的螯合剂连接缀合物，用锡的单粒配方，并证明 rhenium-186 perrhenate迅速而特定的标签。这些放射性释放肿瘤小鼠的生物免疫共轭物的生物分布将确定。目的是产生冻干抗体可以在一步中标记的准备工作以获得具有高免疫反应性和体内保留率的放射免疫偶联物类似于碘抗体。满足这些的产品标准将在医院环境和商业上很容易使用可行。最初的标记实验将使用rhenium-进行 188 perrhenate，很容易从内部的钨 - Rhenium Generator。广泛的动物临床前研究和初始临床研究将在SBIR II期计划中进行。