USE FOR SYNCHROTRON X-RAYS AS BIOMEDICAL RESEARCH TOOLS

基于金属的药物和放射性药物成像剂广泛应用于临床。 使用. 例子包括金基抗关节炎药物和锝 骨扫描剂 高通量的白色X射线， 来自电子储存环的同步加速器辐射使得激发 新的实验来表征这些材料的生物相关性 样品 EXAFS和XANES（扩展X射线吸收发现结构， X射线吸收近边结构）光谱允许通过 邻原子类型、邻原子数和键长的确定 在吸收剂原子（intiarthritis药物代谢物中的金， 例如，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， 金与溶酶体水解酶结合，形式的表征 一些新的抗癌金基材料被肠道吸收， 随后的代谢产物。 将使用低温EXAFS数据 测定新鲜骨表面Tc骨显像剂的结合 以及RE 186缓解剂与骨肿瘤的结合。 一 补充技术WAXS/DAX（广角X射线散射/微分 异常散射）将用于确定更长距离的结构 信息比第一和第二协调领域中的信息更少。 这 这种技术已被物理学家应用于二元合金的研究， 将被用来阐明在几种形式的金属安排， 金属硫蛋白。 据称聚合的锝和锝 还将研究二膦酸盐络合物。 这些优点 技术，正如我们的初步研究所示，它们可以用于 在任何样品如无定形固体、细胞膜或组织上， 他们证明了感兴趣的原子的直接结构信息， 这些样品。 对物种的详细分子理解 在生物/医学环境中存在。 这些技术将 提供这些信息， 这些材料可用于提供更有效的药物和成像 剂.

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.