DEVELOPMENT OF RADIATION SYNOVECTOMY IN ARTHRITIS

关节炎放射滑膜切除术的进展

• 批准号: 3157408
• 负责人: CLEMENT B SLEDGE
• 金额: $ 29.37万
• 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/3157408
• 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.

放射滑膜切除术可对发炎部位进行功能性消融 关节内短程给药后的滑膜， 发射β的放射性同位素。 同位素复合成 颗粒载体以延迟和减少泄漏 关节，从而减少全身辐射暴露。 我们开发了一种用于放射滑膜切除术的新剂 - 镝-165-氢氧化铁大聚集体 (165Dy-FHMA) - 和 过去六年来一直在临床试验中使用它。 112 个膝关节中的 95 个 (85%) 表现出明显的类风湿性膝关节症状 治疗一年后好转。 放射性泄漏 来自治疗关节的剂量少于注射剂量的 1%。 我们建议对 165Dy-FHMA 进行前瞻性试验以确认 我们之前的非对照研究表明了疗效。 预期这些研究会产生有利的结果，并且 认识到 165Dy 的半衰期不切实际，我们建议 开发适合在不适用的领域使用的新药剂 毗邻反应堆，大大扩展了该系统的可用性 治疗。 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动物模型中进行研究。 潜在的同位素包括铼 188 和钇 90；运营商 包括 FHMA、硫胶体和亲脂性复合物。 除了对膝关节类风湿性关节炎有用之外 （以及可能的其他关节），我们的初步研究 血友病膝关节病和色素沉着绒毛结节 滑膜炎表明很有可能 放射滑膜切除术也可用于治疗这些疾病。 治疗效果仍需客观评价 有问题的；为了解决这个问题，我们建议继续 铟-111扫描作为临床有用的研究， 客观、定量的炎症指标 滑膜组织。

项目成果

Use of liposomes as carriers for radiation synovectomy.

使用脂质体作为放射滑膜切除术的载体。

• DOI: 10.1016/0883-2897(88)90081-5
• 发表时间: 1988
• 期刊: International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
• 作者: Zalutsky,MR;Noska,MA;Gallagher,PW;Shortkroff,S;Sledge,CB
• 通讯作者: Sledge,CB

Inhibition of cartilage breakdown by hydrocortisone in a tissue culture model of rheumatoid arthritis.

在类风湿关节炎组织培养模型中氢化可的松抑制软骨破坏。

• DOI: 10.1136/ard.42.3.323
• 发表时间: 1983
• 期刊: Annals of the rheumatic diseases
• 影响因子: 27.4
• 作者: Steinberg,JJ;Kincaid,SB;Sledge,CB
• 通讯作者: Sledge,CB

Evaluation of indium-111 chloride as a radiopharmaceutical for joint imaging in a rabbit model of arthritis.

氯化铟 111 作为放射性药物用于兔关节炎模型关节成像的评价。

• DOI: 10.1097/00004424-198709000-00007
• 发表时间: 1987
• 期刊: Investigative radiology
• 影响因子: 6.7
• 作者: Zalutsky,MR;deSousa,M;Venkatesan,P;Shortkroff,S;Zuckerman,J;Sledge,C
• 通讯作者: Sledge,C

Effects of isolated rheumatoid synovial cells on cartilage degradation in vitro.

分离的类风湿滑膜细胞对体外软骨降解的影响。

• DOI: 10.1002/jor.1100080306
• 发表时间: 1990
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Keller,K;Shortkroff,S;Sledge,CB;Thornhill,TS
• 通讯作者: Thornhill,TS

Radiation synovectomy with 165Dy-FHMA: lymph node uptake and radiation dosimetry calculations.

165Dy-FHMA 放射滑膜切除术：淋巴结摄取和放射剂量测定计算。

• DOI: 10.1016/s0047-0740(86)80008-0
• 发表时间: 1986
• 期刊: International journal of nuclear medicine and biology
• 作者: Zalutsky,MR;Venkatesan,PP;English,RJ;Shortkroff,S;Sledge,CB;Adelstein,SJ
• 通讯作者: Adelstein,SJ