EFFICACIOUS SKELETAL IMAGING RADIOPHARMACEUTICALS

高效液相分析表明， 99mTc-二磷酸盐骨骼显像剂不是纯化学物种， 而是氚-双膦酸络合物的复杂混合物。 这个项目的重点是确定到底是哪一个独立的 金属-双膦酸络合物是这两种药物最有效的试剂 诊断和治疗性核医学应用。这将是 通过研究完成了无机盐学科之间的桥梁 化学、分析化学、放射学、核医学和 医药。制备金属二膦酸根的制备条件 显像剂将多种多样，以利于生产特定的 金属-双膦酸络合物，然后用高效液相色谱分离 组分复合体。这些高效液相分离的成分将在 (A)正常骨骼摄取与软组织摄取的动物模型 组织，以及(B)对异常骨的摄取(创伤诱导的成骨 模型)相对于正常骨骼的摄取。那些被孤立的人 出现最多的含99m-Tc或186-RE的金属-二膦酸络合物 在动物模型中有效的将作为人类诊断试剂进行评估 已确诊为骨转移疾病的患者。“即时工具包” 将开发配方，其中最佳的产量 最大限度地利用了99mTc-双膦酸盐诊断剂。完全的治疗方法 可以通过一种药物传递到转移的骨癌部位的剂量 含有186-Re、32-P或33-P的分离金属-双膦配合物 通过外部、共轭视角、患者计数来估计 接收的诊断剂量的分离组件，并通过热释光 动物模型中的剂量学研究。具有相应功能的组件 放射性照相和剂量学特性将被评估为缓解性 治疗药物对人类转移性疾病患者的影响 对传统疗法不起作用的骨骼。

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.