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RADIODIAGNOSIS OF SCCL WITH ANTIBODIES TO NEUROPHYSINS

使用神经物理素抗体对 SCCL 进行放射诊断

基本信息

批准号：
3189838
负责人：
WILLIAM G NORTH
金额：
$ 10.7万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1993-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3189838
关键词：
antigen antibody reaction histochemistry /cytochemistry image enhancement immunochemistry immunocytochemistry iodine laboratory mouse laboratory rabbit laboratory rat monoclonal antibody neoplasm /cancer radiodiagnosis neurophysins radiodiagnosis radionuclides radiotracer small cell lung cancer

项目摘要

The purpose of this project is to determine the contribution that antibodies to human neurophysins can make to radiodiagnosis of small-cell carcinoma of the lung (SCCL). Human neurophysins (HNPs) are produced by most SCCL tumors, and this persistent property leads to the generation of surface makers (neurophysin- related antigens, NPRA) that are recognized by antibodies to HNPs. Pilot studies conducted with 131 I-labelled forms of these antibodies indicate they can be employed to effectively radioimage SCCL in all patients with HNP-producing tumors. Specific Aims are directed towards: (i) performing a comprehensive evaluation of 131 I-labelled polyclonal anti-HNPs as radiodiagnostic agents for SCCL with respect to their provision of a sensitive, specific, and informative method of tumor imaging that complements standard methods of diagnosis; (ii) appraising available monoclonal anti-HNPs (and their Fab, Fab' and F(ab')2 fragments) for possible clinical application based on their capacity to bind to SCCL cells in vitro, their ability to provide clear radioimages of tumor xenografts in athymic mice, their specificity for tumor cells, and their biodistribution of clearance; (iii) conducting patient studies with a radiolabelled preparation and monoclonal anti-HNP chosen from animal studies for its potential clinical utility; and (iv) applying our knowledge of HNP biosynthesis and tumor vascular resistance to develop improved methods for radioimaging SCCL tumors with anti-HNPs. Concurrent clinical investigations with polyclonal antibodies and animal studies on monoclonal antibody evaluation will precede the experimental use of monoclonal antibodies in patients and those studies on pharmacological manipulation designed to improve delivery of radionuclide to tumors. Quantitative information on tumor binding of radionuclides, tissue dosimetry, and the tumor specificity of our antibodies will be obtained by gamma-camera bidirectional scintigraphy, radiometric analysis and immunocytochemistry. Antibody binding in vitro will be assessed by cytofluorometry and radiometric analysis. A chronically catheterized conscious rat preparation will be employed for biodistribution and clearance studies. The proposed research is expected to lead not only to the adoption of anti-HNPs as valuable diagnostic agents, but also to their eventual use in the therapeutic management of SCCL.

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