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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.

该项目的目的是确定抗人类神经内科药物抗体可用于放射诊断小细胞肺癌(SCCL)。人类神经内科药物 (HNPs)是由大多数SCCL肿瘤产生的，并且这种持久性财产导致了表面标记物的产生(神经物理- 相关抗原，NPRA)，由抗体识别 HNPs。用131种碘标记的形式进行的初步研究抗体表明，它们可以有效地用于所有产生HNP的肿瘤患者的放射影像SCCL。具体目标是：(I)执行 131I标记多克隆抗HNPs的综合评价作为SCCL的放射诊断剂一种灵敏、特异、信息量大的肿瘤成像方法这是对标准诊断方法的补充；(2)评估现有的抗HNPs单抗及其Fab、Fab‘和F(ab’)2 片段)用于可能的临床应用在体外与SCCL细胞结合的能力，它们提供裸鼠移植瘤的清晰放射影像，其肿瘤细胞的特异性及其清除的生物分布； (3)使用放射性标记制剂进行患者研究和从动物研究中选择的抗HNP的单抗潜在的临床效用；以及(Iv)应用我们对HNP的知识生物合成与肿瘤血管耐受性发展改善抗HNPs对小细胞肺癌的放射成像方法。多克隆抗体和多克隆抗体的同步临床研究对单抗的动物研究将在评估之前进行单抗在患者和患者体内的实验应用旨在提高药理作用的研究将放射性核素输送到肿瘤。关于以下方面的定量信息肿瘤与放射性核素的结合、组织剂量学与肿瘤我们的抗体的特异性将通过伽马相机获得双向闪烁照相、放射性分析和免疫细胞化学。将评估抗体在体外的结合情况通过细胞荧光分析和放射分析。一个长期存在的将使用插管清醒大鼠制剂用于生物分布和清除研究。这项拟议的研究预计不仅会导致采用抗HNPs作为有价值的诊断试剂，但也对他们的最终应用于小细胞肺癌的治疗管理。