BIFUNCTIONAL CHELATES IN CANCER IMAGING AND THERAPY

双功能螯合物在癌症成像和治疗中的应用

基本信息

批准号：
3168094
负责人：
DAVID A GOODWIN
金额：
$ 21.19万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-07-01 至 1994-06-30
项目状态：
已结题

项目摘要

The broad long-term goal of this project is to harness the physical and chemical properties of metallic elements to the diagnosis and treatment of cancer. Bifunctional chelating agents are powerful molecules tightly attaching metal ions to biological molecules. Thus the enhanced combined properties of the conjugates can probe specifically, report function, and treat living tumors. Specific aims are to produce new anti-hapten monoclonal antibodies (MoAbs) with high affinity and specificity for the metal chelates of In, Ga, Y, and Tc; to study the biological behavior of new bifunctional monoclonal antibodies having one tumor specific binding site and the other chelate (hapten or biotin) specific; to use these new agents in a novel pretargeted immunoscintigraphy technique in which antibody and radiolabel are given separately, to lower liver and blood background and improve tumor to background ratios; to determine the optimum interval between bifunctional MoAb and radiolabeled hapten or biotin-chelate, determine the effect of "chase" agents and make early images at 1 to 3 hours using Tc-99m and Ga-68 with the ultimate aim of making SPECT and PET tumor images in cancer patients;: to study new macrocyclic chelators for increased in vivo and in vivo stability and kinetic inertness to ligand exchange with In-111, Tc-99m, Ga-68, and Y-90 MoAbs; to use various metabolizable chelate-antibody linkers to increase clearance of background activity via the kidney; to carry out tumoricidal experiments using pretargeting of tumors and Y-90 chelates; to carry out clinical scintillation imaging using both PET and SPECT in human cancer patients with the most promising agents. The Methodology involves hybridoma technology using specially designed antigens, screening mice with radiolabeled antigen, tumor mouse distribution of new bifunctional antibodies with dual specificity for tumor and chelate, use of an avidin- biotin system in a pretargeted immunoscintigraphy method with 1-2 hr images using Tc-99m and Ga-68 and therapy with Y-90. These studies should provide methods for reducing background and improving the effectiveness of monoclonal antibodies in tumor imaging and therapy. These methods will provide the clinician with an "instant kit" that can be labeled with readily available radionuclides economically, for easy application in todays nuclear medicine department.

该项目的长期长期目标是利用物理金属元素的化学特性用于诊断和癌症的治疗。双功能螯合剂很强大将金属离子紧密连接到生物分子上的分子。因此，结合物的增强合并性能可以探测具体而言，报告功能和治疗活性肿瘤。具体的目的是生产新的抗hapten单克隆抗体（MOABS）具有高亲和力和特异性的金属螯合物 ga，y和tc;研究新双功能的生物学行为具有一个特异性结合位点的单克隆抗体和另一个特异性的螯合物（触觉或生物素）；使用这些新的在一种有预定的免疫智能技术的新型特工中，其中分别给出抗体和放射性标记，以降低肝脏和血液背景并改善肿瘤与背景比率；到确定双功能摩押和放射性标记的触发或生物素 - 氯酸盐，确定 “追逐”代理商使用TC-99M在1至3小时制作早期图像 GA-68的最终目的是制造SPECT和PET肿瘤癌症患者的图像；：研究新的大环螯合剂体内和体内稳定性和动力学惰性提高到与IN-111，TC-99M，GA-68和Y-90摩押的配体交换；使用各种可代谢的螯合抗体接头增加通过肾脏清除背景活动；进行使用肿瘤和Y-90的预先定位的肿瘤实验螯合物；使用两者都进行临床闪烁成像人类癌症患者的宠物和SPECT最有前途的代理商。该方法涉及使用杂交瘤技术特殊设计的抗原，用放射性标记的小鼠筛选小鼠抗原，新双功能抗体的肿瘤小鼠分布具有对肿瘤和螯合的双重特异性，使用Avidin- 生物素系统以1-2 使用TC-99M和GA-68以及Y-90治疗的HR图像。这些研究应提供减少背景和提高单克隆抗体在肿瘤中的有效性成像和治疗。这些方法将为临床医生提供可以随时可用的“即时套件” 放射性核素在经济上，在当今的核中易于应用医学系。