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: 3288090
• 负责人: RICHARD C ELDER
• 金额: $ 8.67万
• 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 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3288090
• 关键词: X ray; antiarthritic agent; antineoplastics; 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.

金属基药物和放射性显像剂广泛应用