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.

该项目的目的是确定人类神经植物的抗体可以使肺的小细胞癌（SCCL）。人类神经细胞（HNP）由大多数SCCL肿瘤产生，并且这种持久性属性导致表面制造商的产生（神经蛋白酶 - 相关的抗原，NPRA），通过抗体识别 HNP。使用131个I标记形式进行的试点研究抗体表明可以有效地使用它们所有产生HNP的肿瘤患者的放射图SCCL。具体目标是针对以下方面的：（i）执行 131个I标记的多克隆抗HNP的全面评估作为SCCL的放射性诊断剂相对于其提供肿瘤成像的敏感，特异性和信息丰富的方法这补充了标准的诊断方法；（ii）评估可用的单克隆抗HNP（以及他们的Fab，Fab'and F（AB'）2 片段），以基于他们的临床应用在体外与SCCL细胞结合的能力，它们提供的能力无胸腺小鼠中肿瘤异种移植的清晰放射图，它们肿瘤细胞的特异性及其对清除的生物分布；（iii）进行放射性标记的制剂进行患者研究从动物研究中选择的单克隆抗HNP 潜在的临床公用事业；（iv）应用我们对HNP的了解生物合成和肿瘤血管抗性的发展用抗HNP的放射现象的SCCL肿瘤的方法。以及多克隆抗体的同时临床研究和关于单克隆抗体评估的动物研究将在在患者中的单克隆抗体的实验用途旨在改善的药理操作的研究放射性核素递送到肿瘤。定量信息放射性核素，组织剂量法和肿瘤的肿瘤结合我们的抗体的特异性将通过伽马相机获得双向闪烁显像，辐射分析和免疫细胞化学。将评估体外抗体结合通过细胞荧光测定法和辐射分析。长期将采用导管插入意识的老鼠准备生物分布和清除研究。拟议的研究预计不仅会导致采用反HNP作为有价值的诊断剂，但也最终用于SCCL的治疗管理。