EFFICACIOUS SKELETAL IMAGING RADIOPHARMACEUTICALS

有效的骨骼成像放射性药物

• 批准号: 3170728
• 负责人: EDWARD A DEUTSCH
• 金额: $ 17.56万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170728
• 关键词: blood chemistry; bone imaging /visualization /scanning; bone neoplasms; calcium disorder; diagnosis quality /standard; diphosphonate; electrochemistry; high performance liquid chromatography; human tissue; metal complex; neoplasm /cancer radionuclide diagnosis; nuclear medicine; oxidation; pathologic ossification; radionuclide diagnosis; radiopharmacology; reagent /indicator; technetium; thin layer chromatography; tin

High-performance liquid chromatographic (HPLC) analysis has shown that 99mTc-diphosphonate skeletal imaging agents are not pure chemical species, but rather are complicated mixtures of technetium-diphosphonate complexes. The focus of this project is the determination of exactly which isolated metal-diphosphonate complexes are the most effective agents for both diagnostic and therapeutic nuclear medicine applications. This will be accomplished through research bridging the disciplines of inorganic chemistry, analytical chemistry, radiology, nuclear medicine, and medicine. Preparative conditions used to generate metal-diphosphonate imaging agents will be varied in order to favor the production of specific metal-diphosphonate complexes, and then HPLC will be used to isolate these component complexes. These HPLC isolated components will be evaluated in animal models for (a) uptake on normal bone relative to uptake in soft tissues, and (b) uptake on abnormal bone (trauma-induced osteogenesis model) relative to uptake on normal bone. Those isolated metal-diphosphonate complexes containing 99m-Tc or 186-RE which appear most effective in animal models will be evaluated as diagnostic agents in human patients with established metastatic disease to bone. "Instant kit" formulations will be developed in which the yields of the optimum 99mTc-diphosphonate diagnostic agents are maximized. The total therapeutic dose that could be delivered to a metastatic bone cancer site by an isolated metal-diphosphonate complex containing 186-Re, 32-P or 33-P will be estimated by external, conjugate view, counting of patients who have received diagnostic doses of isolated components, and by thermoluminescent dosimetry in animal models. Those components with appropriate scintigraphic and dosimetric properties will be evaluated as palliative therapeutic agents in human patients suffering from metastatic disease to the bone that is not-responsive to conventional therapy.

高效液相色谱（HPLC）分析表明， 99 mTc-二膦酸盐骨骼显像剂不是纯化学物质， 而是锝-二膦酸盐络合物的复杂混合物。 这个项目的重点是确定究竟是哪一个孤立的 金属二膦酸盐络合物是最有效的药物， 诊断和治疗核医学应用。 这将是 通过研究完成的桥梁学科无机 化学、分析化学、放射学、核医学，以及 药 用于生成金属二膦酸盐的分解条件 成像剂将变化以有利于产生特异性的 金属-二膦酸盐络合物，然后使用HPLC分离这些 组分络合物 这些HPLC分离组分将在 （a）相对于在软组织中的摄取，在正常骨上的摄取 组织，和（B）异常骨（创伤诱导的骨生成）上的摄取 模型）相对于正常骨上的摄取。 分离的那些 含99 m-Tc或186-RE的金属二膦酸盐配合物， 在动物模型中的有效性将被评估为人类的诊断剂 已确诊骨转移性疾病的患者。 “即时工具包” 将开发配方，其中最佳的产量 最大化99 mTc-二膦酸盐诊断剂。 的总治疗 可以通过一种药物递送至转移性骨癌部位的剂量 含有186-Re、32-P或33-P的分离的金属-二膦酸盐络合物将 通过外部、共轭视图估计， 接受诊断剂量的隔离成分，并通过热释光 动物模型中的剂量测定。 这些组件具有适当的 放射学和剂量测定特性将被评价为姑息性 在患有转移性疾病的人类患者中的治疗剂， 对传统疗法无反应的骨头。