THE ROLE OF HUMAN FERRITIN IN THE LOCALIZATION OF GA-67

人铁蛋白在 GA-67 定位中的作用

• 批准号: 3185695
• 负责人: RONALD E. WEINER
• 金额: $ 5.21万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-03-15 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185695
• 关键词: adenosine triphosphate; drug design /synthesis /production; ferritin; lactoferrin; macromolecule; macrophage; radiopharmacology; transferrin

The long-term objectives of this project are to understand the localization mechanism of the tumor and abscess localizing radiopharmaceutical, Ga-67, in order to develop strategies to improve its diagnostic efficacy and devise new techniques which may supplant or replace it. The knowledge gained from this project should serve as a model for the rational design of future agents and may provide some insight into tumor physiology. This knowledge may also help to improve the therapeutic efficacy of gallium nitrate (NCI 15200) now in Phase I clinical trials. Specifically, we wish to investigate the role of human ferritin lactoferrin (LF) and transferrin (TF) in nuclide localization. We plan to fully characterize the affinity of these macromolecules for Ga-67 using purified protein preparations and examining varius factors found intracellularly which may modulate this affinity. Of particular importance is understanding the mechanism of action of various phosphate containing compounds, e.g., ATP, which we have previously shown promote in vitro the translocation of nuclide between LF or TF to horse ferritin. With the knowledge gleaned from these experiments, we plan to investigate the role of these proteins in nuclide uptake in human monocytes and macrophages as a model system and how the concentration of cytoplasmic constituents, such as ATP, affect uptake. Lastly, we will explore how other nuclides are bound and translocated in this model system. We shall focus primarily on those nuclides which could replace Ga-67 as an abscess or tumor imaging agent. We hope to apply the HPLC technique to characterize the affinities of these macromolecules under a variety of conditions. If not, standard protein chromatographic procedures will be used. We will use the new Percoll gradient technique, which isolates monocytes and lymphocytes according to their density differences.

本项目的长期目标是了解本地化 肿瘤和脓肿定位放射性药物Ga-67的机制， 为了制定战略，以提高其诊断效率， 设计新的技术，可能取代或取代它。知识 从这个项目中获得的应该作为一个模型的合理设计 未来的药物，并可能提供一些深入了解肿瘤生理学。 这 知识也可能有助于提高镓的治疗效果 硝酸盐（NCI 15200）目前正在进行I期临床试验。 具体来说，我们希望 研究人铁蛋白、乳铁蛋白（LF）和转铁蛋白在 (TF)在核素定位中。 我们计划全面描述 这些大分子的Ga-67使用纯化的蛋白质制剂， 检查细胞内发现的各种可能调节这一点的因子， 亲和力 特别重要的是了解 各种含磷酸盐的化合物，例如，ATP，我们有 先前显示，在体外促进LF之间的核素易位 或TF为马铁蛋白。 从这些人身上收集到的知识 实验中，我们计划研究这些蛋白质的作用， 作为模型系统的人单核细胞和巨噬细胞的摄取以及 细胞质成分如ATP的浓度影响摄取。 最后，我们将探讨其他核素是如何结合和易位， 这个模型系统。 我们将主要关注那些可能 取代Ga-67作为脓肿或肿瘤显像剂。 我们希望应用 HPLC技术，以表征这些大分子在 各种条件。 如果不是，则标准蛋白质色谱 程序将被使用。 我们将使用新的Percoll梯度技术， 根据单核细胞和淋巴细胞的密度 差异

项目成果

Relationship between colorectal liver metastases and CEA levels in gallbladder bile.

结直肠肝转移与胆囊胆汁中 CEA 水平的关系。

• DOI: 10.1097/00000658-198910000-00011
• 发表时间: 1989
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: Yeatman,TJ;Bland,KI;Copeland3rd,EM;Hollenbeck,JI;Souba,WW;Vogel,SB;Kimura,AK
• 通讯作者: Kimura,AK

Role of phosphate-containing compounds in the transfer of indium-111 and gallium-67 from transferrin to ferritin.

含磷酸盐化合物在铟 111 和镓 67 从转铁蛋白转移到铁蛋白中的作用。

• 发表时间: 1989
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Weiner,RE