Radiation synovectomy produces functional ablation of the inflamed synovium by the intra-articular administration of short-range, beta-emitting isotopes in particulate form to delay leakage from the joint and undesirable distant effects. We have developed a new isotope-particle system, dysprosium-165-ferric hydroxide macroaggregate (165Dy-FHMA), and have demonstrated extremely low levels of leakage from animal and human joints. Clinical trials of effectiveness in humans are underway. We propose to continue clinical trials with Dy-FHMA to establish the effectiveness of this agent in reducing pain, swelling and inflammation in rheumatoid arthritis. Other isotopes and other carrier systems will be evaluated to provide increased availablility, widened spectrum of tissue penetration for use in various joints, and new carriers to retain the administered isotope with the joint. Liposomes, albumin microspheres, nd colloids will be examined as well as continued investigation of the usefulness of FHMA with other isotopes. Essential to the demonstration of usefulness of these techniques is the development of objective means of assessing joint inflammation before and after treatment. In animals, antigen-induced arthritis will be used as a model of rheumatoid arthritis and the effect of treatment measured by determination of synovial production of the newly described messenger molecule catabolin. In both animals and humans, external measurement of joint temperature using thermography will be compared with radionuclide scans using (99m)Tc compounds.
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