USE OF SYNCHROTRON X-RAYS AS BIOMEDICAL RESEARCH TOOLS

使用同步加速器 X 射线作为生物医学研究工具

• 批准号: 3288089
• 负责人: RICHARD C ELDER
• 金额: $ 8.44万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-12 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3288089
• 关键词: X ray; antiarthritic agent; chemical structure function; chemical synthesis; diphosphonate; gold; hydrolase; lysosomes; metallothionein; neoplasm /cancer pharmacology; organometallic compounds; radiopharmacology; skeletal neoplasm

Metal-based drugs and radiopharmaceutical imaging agents are in widespread use. Examples include the gold-based antiarthritis drugs and technetium bone scanning agents. The high flux of white X-rays available as synchrotron radiation from an electron storage ring makes possible exciting new experiments to characterize these materials in biologically relevant samples. EXAFS and XANES (extended X-ray absorption find structure and X-ray absorption near edge structure) spectroscopies allow speciation via determination of neighbor atom type, number of neighbors and bond lengths between the absorber atom (gold in an intiarthritis drug metabolite, for example) and its neighbors. Data collected at liquid nitrogen temperature will improve the resolution of these experiments and allow determination of gold binding to lysosomal hydrolases, the characterization of the form of some new anticancer gold-based materials absorbed by the intestine and the subsequent metabolic products. Low temperature EXAFS data will be used to determine the binding of Tc bone imaging agents on fresh bone surfaces and the binding of rhenium (Re186) palliatives to skeletal tumors. A complementary technique WAXS/DAX (wide angle X-ray scattering/differential anomalous scattering) will be used to determine more long range structural information than that in the first and second coordination sphere. This technique which has been applied by physicists to studies of binary alloys, will be used to elucidate the metal arrangement in several forms of metallothioneins. The purportedly polymeric technetium and rhenium diphosphonate complexes will be studied also. The advantages of these techniques, as shown in our preliminary studies, are that they can be used on any sample such as an amorphous solid, a cell membrane or tissue and that they proved direct structural information on the atoms of interest in these samples. A detailed molecular understanding of the species actually present in the biological/medical milieu is needed. These techniques will provide that information such that intelligent chemical modification of these materials can be used to provide more efficacious drugs and imaging agents.

基于金属的药物和放射性药物显像剂广泛存在 使用。例如，含金的抗关节炎药物和氚。 骨骼扫描剂。白X射线的高通量可以作为 来自电子存储环的同步辐射使激发成为可能 新的实验来表征这些材料在生物学上的相关性 样本。EXAFS和XANES(扩展X射线吸收发现结构和 X射线吸收近边结构)光谱允许物种通过 近邻原子类型、近邻数目和键长的确定 在吸收原子(关节炎药物代谢物中的金，用于 例如)和它的邻居。在液氮温度下收集的数据 将提高这些实验的分辨率，并允许确定 金与溶酶体水解酶的结合形式的表征 一些新的抗癌金基材料被肠道吸收和 随后的代谢产物。将使用低温EXAFS数据 新鲜骨显像剂与新鲜骨表面结合力的测定 以及Re(Re186)缓释剂与骨肿瘤的结合。一个 辅助技术WAXS/DAX(广角X射线散射/差分 异常散射)将被用来确定更远距离的构造 信息多于第一和第二个配位圈中的信息。这 物理学家用来研究二元合金的技术， 将被用来阐明金属排列的几种形式 金属硫蛋白。据称是聚合态的氚和铼 双膦酸络合物也将被研究。这些产品的优势 正如我们的初步研究所表明的那样，技术是可以使用的 在任何样品上，如无定形固体、细胞膜或组织，以及 他们证明了关于感兴趣的原子的直接结构信息 这些样本。对该物种的详细分子理解实际上 在生物/医学环境中存在是必要的。这些技术将 提供这样的信息，即智能化学修饰 这些材料可以用来提供更有效的药物和成像 探员们。