THE DEVELOPMENT OF RADIATION SYNOVECTOMY IN ARTHRITIS

关节炎放射滑膜切除术的进展

• 批准号: 3157407
• 负责人: CLEMENT B SLEDGE
• 金额: $ 27.73万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3157407
• 关键词: allergic arthritis; articular cartilage; bioassay; clinical trials; disease /disorder model; histopathology; human subject; human therapy evaluation; laboratory rabbit; musculoskeletal disorder diagnosis; radiation therapy dosage; radiobiology; radiological health; radionuclide imaging /scanning; radionuclide therapy; radiopharmacology; rheumatoid arthritis; skeletal pharmacology; thermometry

Radiation synovectomy produces functional ablation of inflamed synovium following intra-articular administration of short-range, beta-emitting radioisotopes. The isotope is complexed to a particulate carrier in order to delay and decrease leakage rom the joint, thereby reducing the total body radiation exposure. We have developed a new agent for radiation synovectomy - dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) - and have been using it in clinical trials over the past six years. Ninety-five of 112 (85%) rheumatoid knees showed significant improvement one year after treatment. Leakage of radioactivity from the treated joint has been less than 1% of the injected dose. We propose to conduct a prospective trial of 165Dy-FHMA to confirm the efficacy indicated in our previous uncontrolled studies. Anticipating a favorable outcome from these studies, and recognizing the impractical half life of 165Dy, we propose to develop new agents that will be appropriate for use in areas not adjacent to a reactor, greatly extending the availability of this therapy. Other isotopes and carrier systems, in various combinations, will be investigated in the animal model of antigen-induced arthritis. Potential isotopes include rhenium 188 and yttrium-90; carriers include FHMA, sulfur colloids and lipophilic complexes. In addition to its usefulness in rheumatoid arthritis of the knee (and potentially other joints), our preliminary studies in hemophilic arthropathy of the knee and pigmented villonodular synovitis indicate a high degree of probability that radiation synovectomy will be useful in these disorders as well. Objective evaluation of the efficacy of treatment remains problematic; to address this problem, we propose to continue our investigation of indium-111 scanning as a clinically useful, objective and quantitative indicator of inflammation in the synovial tissues.

放射性滑膜切除术产生功能性消融炎症 关节内施用短程， β放射性同位素 同位素络合成 颗粒载体，以延迟和减少泄漏 从关节，从而减少全身辐射暴露。 我们开发了一种新的放射性滑膜切除剂- 镝-165-氢氧化铁大团聚体（165 Dy-FHMA）-和 在过去的六年里一直在临床试验中使用它。 112个类风湿性膝关节中的95个（85%）显示出显著的 治疗一年后好转。 放射性泄漏 从治疗的关节已经小于注射剂量的1%。 我们建议对165 Dy-FHMA进行前瞻性试验，以证实 在我们之前的非对照研究中显示的疗效。 预期这些研究的结果良好，以及 认识到165 Dy的半衰期不切实际，我们建议 开发新的制剂，适用于不 与反应堆相邻，极大地扩展了这种 疗法 其他同位素和载体系统，以各种组合，将 在抗原诱导的关节炎的动物模型中进行研究。 可能的同位素包括1880和钇-90; 包括FHMA、硫胶体和亲脂复合物。 除了对膝关节类风湿性关节炎有用外 (and潜在的其他关节），我们的初步研究 血友病性膝关节病和色素沉着绒毛结节性 滑膜炎表明， 放射性滑膜切除术在这些疾病中也是有用的。 客观评价治疗效果 为解决这一问题，我们建议继续 铟-111扫描作为临床上有用， 炎症的客观和定量指标， 滑膜组织