Abstract
Radiation synovectomy is a potential weapon in the therapeutic armamentarium of nuclear medicine. It is an attractive alternative to surgical or chemical synovectomy for the treatment of rheumatoid arthritis. In this article the clinical results obtained with radiation synovectomy from the 1950s through 1992 are summarized and reviewed. Even after taking into account the paucity of well-controlled trials and rigorous clinical follow-up, it is clear that radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radioactivity from the treated joint, and the resulting high doses that can be delivered to nontarget organs. New approaches to the preparation of radiolabeled particles for use in radiation synovectomy promise to minimize this leakage and thus allow the full potential of this important radiotherapy to be realized.
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Hoefnagel CA. Anti-cancer radiopharmaceuticals. Anti-Cancer Drugs 1991;2: 107–132
Harbert JC. Nuclear medicine therapy. New York: Thieme Medical, 1987
Spencer RP. Therapy in nuclear medicine. New York: Grune & Stratton, 1978
Rosenthall L. Use of radiocolloids for intra-articular therapy for synovitis. In: Spencer RP, ed. Therapy in nuclear medicine. New York: Grune & Stratton; 1978: 147–242
Harbert JC. Radiocolloid therapy in joint diseases. In: Harbert JC, ed. Nuclear medicine therapy. New York: Thieme Medical; 1987: 169–186
Doherty M. Potential rheumatologic applications of intra-articular radiocolloid therapy. Geriatric Medicine Today 1984;3: 31–42
Gschwend N. Synovectomy. In: Kelly WN, Harris ED, Ruddy S, Sledge CB, eds. Textbook of rheumatology. Philadelphia: Saunders; 1989;1934–1961
Zuckerman JD, Sledge CB, Shortkroff S, Venkatesan P. Treatment of rheumatoid arthritis using radiopharmaceuticals. Nucl Med Biol 1987;14: 211–218
Sledge CB, Noble J, Hnatowich DJ, Kramer R, Shortkroff S. Experimental radiation synovectomy by 165-Dy ferric hydroxide macroaggregate. Arthritis Rheum 1977;20: 1334–1342
Chinol M, Vallabhajosula S, Goldsmith SJ, Klein MJ, Deutsch KF, Chinen LK, Brodack JW, Deutsch EA, Watson BA, Tofe AJ. Chemistry and biological behavior of samarium-153 and rhenium-186-labeled hydroxyapatite particles: potential radiopharmaceuticals for radiation synovectomy. J Nucl Med 1993;34:1536–1542
Shortkroff S, Mahmood A, Sledge CB, Jones AG, Brodack JW, Chinen LK, Deutsch E, Deutsch KF. Studies on Ho-166-labeled hydroxyapatite: a new agent for radiation synovectomy. J Nucl Med 1992;33: 937
Brodack JW, Chinen LK, Deutsch E, Deutsch KF. Studies on the radiolabeling of hydroxyapatite particles for use as radiation synovectomy agents. J Nucl Med 1992;33: 980
Hosain F. Intraarticular therapy with radionuclides. In: Spencer RP, Seevers RH, Friedman AM, eds. Radionuclides in therapy. Boca Raton, Florida: CRC Press; 1987: 83–89
Menkes CJ, Tubiana R, Galmiche B, Delbarre F. Intra-articular injection of radioisotopic beta emitters: application to the treatment of the rheumatoid hand. Orthop Clin North Am 1973;4: 1113–1125
Hosain F, Haddon MJ, Hosain H, Drost JK, Spencer RP. Radiopharmaceuticals for diagnosis and treatment of arthritis. Nucl Med Biol 1990;17: 151–155
Calabro JJ. Rheumatoid arthritis: diagnosis and management. Clin Symp 1986;38: 1–32
NIH Conference on Rheumatoid Arthritis: evolving concepts of pathogenesis and treatment. Ann Intern Med 1984;101: 810–824
Newsweek March 20;64–70, 1989
Von Reis G, Swensson A. Intra-articular injections of osmic acid in painful joint affections. Acta Med Scand [Suppl] 1951; 259:27–32
Behrens F, Shepard N, Mitchell N. Metabolic recovery of articular cartilage after intra-articular injections of gluco-corticoid. J Bone Joint Surg [Am] 1976;58: 1157–1160
Mori M. A review of knee joint synovectomy in rheumatoid arthritis with theoretical and technical considerations. Ann Chir Gynaecol 1985;74: 40–47
English RJ, Zalutsky M, Venkatesan P, Sledge CB. Therapeutic application of dysprosium-165-FNMA in the treatment of rheumatoid knee effusions. J Nucl Med Tech 1986;14: 18–20
Noble J, Jones AG, Davis MA, Sledge CB, Kramer RI, Livni E. Leakage of radioactive particle systems from a synovial joint studied with a gamma camera: its application to radiation synovectomy. J Bone Joint Surg [Am] 1983;65: 381–389
Ansell BM, Crook A, Mallard JR, Bywaters EGL. Evaluation of intra-articular colloidal gold Au 198 in the treatment of persistent knee effusions. Ann Rheum Dis 1963;22: 435–439
Delbarre F, Menkes CJ, Aignan M, Roucayrol JC, Ingrand J, Sanchez A. Une nouvelle préparation radioactive pour la synoviorthèse: le rhénium-186 colloïdal. Advantages par rapport au colloïde d'or-198. Nouv Presse Med 1973;2: 1372
Bowen BM, Darracott J, Garnett ES, Tomlinson RH. Yttrium-90 citrate colloid for radioisotope synovectomy. Am J Hosp Pharm 1975;32: 1027–1030
Winston MA, Bluestone R, Cracchiolo A 3rd, Blahd WH. Radiation synovectomy with 32-P-chromic phosphate —kinetic studies. J Nucl Med 1973;14: 886–889
Onetti CM, Gutierreze E, Hliba E, Aguirre CR. Synoviorthesis with 32-P-colloidal chromic phosphate in rheumatoid arthritis — clinical, histopathologic and arthrographic changes. J Rheumatol 1982;9: 229–238
Menkes C-J, Le Gô A, Verrier P, Aignan M, Delbarre F. Double-blind study of erbium 169 injection (synoviorthesis) in rheumatoid digital joints. Ann Rheum Dis 1977;36: 254–256
Virkkunen M, Krusium FE, Heiskanen T. Experiences of intra-articular administration of radioactive gold. Acta Rheum Scand 1967;13: 81–91
Gumpel JM, Beer TC, Crawley JCW, Farran HEA. Yttrium 90 in persistant synovitis of the knee — a single centre comparison. The retention and extra-articular spread of four 90Y radiocolloids. Br J Radiol 1975;48: 377–381
Oka M, Rekonen A, Ruotsi A, Seppälä O. Intra-articular injection of Y-90 resin colloid in the treatment of rheumatoid knee joint effusions. Acta Rheum Scand 1971;17: 148–160
Szymendera J, Kaminska J, Radwan M, Zoltowski T. PVP-stabilized indium sulphide colloid for liver and spleen scanning. Br J Radiol 1969;42: 944–945
Szymendera J, Zoltowski T, Radwan M, Kaninska J. Chemical and electron microscope observations of a safe PVP-stabilized colloid for liver and spleen scanning. J Nucl Med 1971;12: 212–215
Szymendera J, Radwan M. Rhenium and technetium heptasulfide. Letters to the editors. Author's reply. J Nucl Med 1971;13:287–288
Patton DD, Garcia EN, Webber MM. Simplified preparation of technetium 99m sulfide colloid for liver scanning. Am J Roentgenol 1966;97: 880–885
Bardy A, Beydon J, Hegesippe M. Préparation du sulfure de rhénium colloïdal marqué par 186 Ré pour utilisation en synoviorthèse. Int J Appl Radiat Isotop 1973;24: 57–60
Venkatesan P, Shortkroff S, Zalutsky MR, Sledge CB. Rhenium heptasulfide: a potential carrier system for radiation synovectomy. Nucl Med Biol 1990;4: 357–362
Hnatowich DJ, Kramer RI, Sledge CB, Noble J, Shortkroff S. Dysprosium-165 ferric hydroxide macroaggregrates for radiation synovectomy. J Nucl Med 1978;19: 303–308
Sledge CB, Atcher RW, Shortkroff S, Anderson RJ, Bloomer WD, Hurson B. Intraarticular radiation synovectomy. Clin Orthop 1984;29: 37–40
Sledge CB, Zuckerman JD, Zalutsky M, Atcher RW, Shortkroff S, Lionberger DR, Rose HA, Hurson BJ, Lankenner PA, Anderson RJ, Bloomer WA. Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium-165-ferric hydroxide macroaggregates. Arthritis Rheum 1986;29: 153–159
Sledge CB, Zuckerman JD, Shortkroff S, Zalutsky MR, Vankatesan P, Snyder MA, Barrett W. Synovectomy of the rheumatoid knee using intraarticular injection of dysprosium-165-ferric hydroxide macroaggregates. J Bone Joint Surg [Am] 1987;69: 970–975
Zalutsky MA, Venkatesan PP, English RJ, Shortkroff S, Sledge CB, Adelstein SJ. Radiation synovectomy with Dy-165 FHMA: lymph node uptake and radiation dosimetry calculations. Int J Nucl Med Biol 1986;12: 457–465
Davis MA, Chinol M. Radiopharmaceuticals for radiation synovectomy: evaluation of two yttrium-90 particular agents. J Nucl Med 1989;30: 1047–1055
Bard DR, Knight CG, Page Thomas DP. The retention and distribution in rabbit knee of a radionuclide complexed with a lipophilic chelator in liposomes. Clin Exp Rheumatol 1983;1: 113–117
Bard DR, Knight CG, Page-Thomas DP. Effect of the intraarticular injection of lutetium-177 in chelator liposomes on the progress of an experimental arthritis in rabbits. Clin Exp Rheumatol 1985;3: 237–242
Zalutsky MR, Noska MA, Gallagher PW. Properties of multilamellar liposomes containing 99mTc04-: effect of distearoylphosphatidy1choline to sphingomyelin ratio. Nucl Med Biol 1986;13: 269–276
Zalutsky MR, Noska MA, Gallagher PW, Shortkroff S, Sledge CB. Use of liposomes as carriers for radiation synovectomy. Nucl Med Biol 1988;15: 151–156
Morphy JR, Parker D, Kataky R, Harrison A, Easton MAW, Millican A, Phipps A, Walker C. Towards tumor targeting with copper-radiolabelled macrocycle-antibody conjugates. J Chem S CH 1989;792
Fritzberg AR, Abrams PG, Beumir PL, Kasina S, Morgan C, Rao TN, Keno JM, Sanderson JA, Srinivasan A, Wilbur DS, Vanderheyden J-L. Specific and stable labeling of antibodies with technetium-99m with a diamide dithiolate chelating agents. Proc Natl Acad Sci USA 1988;85: 4025–4029
Dumonde DK, Glynn LE. The production of arthritis in rabbits by an immunological reaction to fibrin. Br J Exp Patt 1962;43: 373–380
Steinberg ME, McCrae CR, Bersell RA, Cram B. Intra-articular 5-fluorouracil in antigen induced arthritis. J Bone Joint Surg [Am] 1971;53: 514–522
Rosenspire KL, Blau M, Kennedy AC, Green FA. Assessment and interpretation of radiopharmaceuticals joint imaging in an animal model of arthritis. Arthritis Rheum 1981;24: 711–716
Howson PM, Shepard NL, Mitchell NS. Colloidal chromic phosphate 32-P synovectomy in antigen-induced arthritis in the rabbit. Clin Orthop 1988;229: 283–293
Steinberg J, Sledge CB, Noble J, Gillies HB. Dextran sulphate induced arthritis in rabbits. Ann Rheum Dis 1980;39: 387–391
Aaron RK, Sledge CB, Shortkroff S. Experimental arthritis induced by polysaccharide macromolecules. Arthritis Rheum 1987;30: 679–688
Hinckley CC, Bemiller NJ, Strack LE, Russell LD. Osmium carbohydrate polymers as potential antiarthritic drugs. in: Lippard SJ, ed. Platinum, gold and other chemotherapeutic agents. American Chemical Society, 1983
Husak V, Weidermann M, Kral M. Absorbed dose due to beta-rays from radioactive colloids in radiation synovectomy. Phys Med Biol 1973;18: 848–854
Johnson L, Yanch J. Absorbed dose profile for radionuclides of frequent use in radiation synovectomy. Arthritis Rheum 1991;34: 1521–1530
Van Soesbergen RM, Hoefnagel CA, Marcuse HR, Dijkstra PF, Bernelot Moens HJ. Radiosynoviorthesis of the knee: a double-blind trial of 1 versus 5 mCi gold-198. Clin Rheumatol 1988;7: 224–230
Topp JR, Cross EG, FAM AG. Treatment of persistent knee effusions with intra-articular radioactive gold. Can Med Assoc J 1975;112: 1085–1089
Virkkunen M, Krusius FE, Heiskanen T. Experiences of intra-articular administration of radioactive gold. Acta Rheum Scand 1967;13: 81–91
Zalutsky MR, Venkatesan P, English RJ, Shortkroff S, Sledge CB, Adelstein SJ. Radiation synovectomy with 165Dy-FHMA: lymph node uptake and radiation dosimetry calculations. Int J Nucl Med Biol 1985;6: 457–465
Fellinger K, Schmid J. Die lokale Behandlung der rheumatischen Erkrankungen. Wien Z Inn Med 1952;33: 351
Stevenson AC, Bedford J, Dolphin GW, Purrott RJ, Lloyd DC, Hill AGS, Hill HFH, Fumpel JM, Williams D, Scott JT, Ramsey NW, Bruckner FE, Pearn DB D'A. Cytogenetic and scanning study of patients receiving intra-articular injections of gold-198 and yttrium-90. Ann Rheum Dis 1973;32: 112
Dolphin GW. Biological hazards of radiation. Ann Rheum Dis 1973;32: 23
Chapelle A de la, Rekonen A, Oka M, Ruotsi A. Chromosome damage after intra-articular injections of radioactive yttrium. Ann Rheum Dis 1972;31: 508–512
Ruotsi A, Hypén M, Rekonen A, Oka M. Erbium-169 versus triamcinolone hexacetonide in the treatment of rheumatoid finger joints. Ann Rheum Dis 1979;38: 45–47
Brower AC. Radiographic assessment of disease progression in rheumatoid arthritis. Rheum Dis Clin North Am 1991;17: 471–485
Will R, Laing B, Edelman J, Lovegrove F, Surveyor I. Comparison of two yttrium-90 regimens in inflammatory and osteoarthropathies. Ann Rheum Dis 1992;51: 262–265
Tanaka S, Ueo T, Ohnishi N. Clinical effects of radiation synovectomy. J West Pac Orthop Assoc 1978;15: 83–92
Smith T, Crawley JCW, Shawe DJ, Gumpel JM. SPECT using bremsstrahlung to quantify 90Y uptake in Baker's cysts: its application in radiation synovectomy of the knee. Eur J Nucl Med 1988;14: 498–503
Williams ED. Methods of measuring retention of radio-isotopes in the knee and extra-articular spread in vivo. Ann Rheum Dis 1973;32: 13
Fries JF, Williams CA, Ramey D, Bloch DA. The relative toxicity of disease-modifying antirheumatic drugs. Arthritis Rheum 1993;36: 297–306
Boussina I, Toussaint M, Ott H, Hermans P, Fallet G. A double-blind study of erbium 169 synoviorthesis in rheumatoid digital joints. Results after one year. Scand J Rheumatol 1979;8: 71–74
Menkes CJ. Radioisotope synoviorthesis in rheumatoid arthritis. Rheumatol Rehabil 1979;45–46
Ott H, Boussina I, Fallet GH. Synoviorthesis of finger joints using erbium-169. Parameters influencing the clinical results at middle-term. Schweiz Med Woehenschr 1977;107: 1366–1371
Franssen MJAM, Boerbooms AMT, Karthaus RP, Buijs WCAM, van de Putte LBA. Treatment of pigmented villonodular synovitis of the knee with yttrium-90 silicate: prospective evaluations by arthroscopy, histology, and 99mTc pertechnetate uptake measurements. Ann Rheum Dis 1989;48: 1007–1013
Spooren PFMJ, Rasker JJ, Arens RPJH. Synovectomy of the knee with 90Y. Eur J Nucl Med 1985;10: 441–445
Alexieva T, Kunnev K. The treatment of gonarthritis with yttrium-90. Vutr Boles 1990;29: 59–61
Wang SJ, Yeh SH, Kao CH, Lan JL, Chen DY, Lin MS. Treatment of rheumatoid arthritis with Y-90 evaluated by quantitative Tc-99m HMPAO WBC and Ga-67 scan. Eur J Nucl Med 1990;16: S144
Heim M, Horoszowski H, Lieberman L, Varon D, Martinowitz U. Methods and results of radionucleotide synovectornies. Ort Traum oggi 1990;10: 30–32
Erken EHW. Radiocolloids in the management of hemophilic arthropathy in children and adolescents. Clin Orthop 1991;264: 129–135
Deckart H, Tamaschke HJ, Ertl S, Tautz M, Knop G. Radiosynovektomie des Kniegelenkes mit 198Au-kolloid, 90Y-Eisenhydroxyd-kolloid und 118Re-Sulfid-kolloid. Radiobiol Radiother 1979;20: 363–370
Boerbooms AMT, Buijs WCAM, Danen M, van de Putte LBA, Vandenbroucke JP. Radiosynovectomy in chronic synovitis of the knee joint in patients with rheumatoid arthritis. Eur J Nucl Med 1985;10: 446–449
Teuber J, Regler G, Baenkler H. Experiences in the treatment of rheumatoid arthritis with 90-yttrium-silicate. Med Klin 1976;71: 1690–1691
Muller W, Pavelka K, Friedrich R. Treatment of chronic articular effusions with 90-yttrium (90Y). Scand J Rheumatol 1975;4: 216–220
Wang SJ, Kao CH, Chen DU, Lin MS, Yeh SH, Lan JL. Quantitative 99Tcm-HMPAO white blood cells and 67Ga scanning in rheumatoid arthritis. Nucl Med Commun 1991;12: 551–558
Rau R, Schutte H. Results of radiosynoviorthesis with yttrium 90 in chronic synovitis: a long-term prospective study. I. Total results and effect of local factors. Z Rheumatol 1983;42: 265–270
Kyle V, Hazleman BL, Wraight EP. Yttrium-90 therapy and 99mTc pertechnetate knee uptake measurments in the management of rheumatoid arthritis. Ann Rheum Dis 1983;42: 132–137
Hagena FW. Radio- synoviorthesis with yttrium 90 of the knee joint in polyarthritis. Fortschr Med 1982;100: 1673–1677
Teuber J, Baenkler HW, Regler G. Treatment of rheumatoid arthritis with 90yttrium. Follow up studies. Immun Infekt 1978;6: 106–109
Doyle DV, Glass JS, Gow PJ, Daker M, Grahame R. A clinical and prospective chromosomal study of yttrium-90 synovectomy. Rheumatol Rehabil 1977;16: 217–222
Bauer R, Kerschbaumer F, The treatment of chronic knee joint synovitis with radioactive isotopes. Arch Orthop Unfallchir 1976;84: 13–26
Oka M. Radiation synovectomy of the rheumatoid knee with yttrium, 90. Ann Clin Res 1975;7: 205–210
Crone-Munzebrock W, Redeker S. Results in treatment of radiosynoviorthesis by yttrium-90- silicate in patients with chronic polyarthritis. Radiobiol Radiother 1985;26: 813–817
Stojanovic ID. Radiation synovectomy of the knee. Clinical effect, failures and complications. Magy Rheumatol 1981;22: 23–34
Harling OK, Yanch JC, Choi JR, Solares GR, Rogus RD, Moulin DJ, Johnson LS, Olmez I, Wirdzek S, Bernard JA. Boron neutron capture therapy and radiation synovectomy research at the Massachusetts Institute of Technology Research Reactor. Nucl Sci Eng 1992;110: 330–348
Radiation synovectomy still shows promise for RA. Med World News 1988;38.
Vella M, Zuckerman JD, Shortkroff S, Venkatesan P, Sledge CB. Repeat radiation synovectomy with dysprosium 165-ferric hydroxide macroaggregates in rheumatoid knees unresponsive to initial injection. Arthritis Rheum 1988;31: 789–792
Promosing tool for treating arthritic joints. Harvard Medical Area FOCUS 1985; March 7: 1–3
Zuckerman JD, Sledge CB, Shortkroff S, Venkatesan P. Treatment of rheumatoid arthritis using radiopharmaceuticals. Nucl Med Biol 1987;14: 211–218
Sledge CB, Zuckerman JD, Shortkroff S, Zalutsky MR, Venkatesan P, Snyder MA, Barrett WP. Synovectomy of the rheumatoid knee using intra-articular injection of dys prosium-165-ferric hydroxide macroaggregates. J Bone Joint Surg [Am] 1987;69: 970–975
Sledge CB, Zuckerman JD, Zalutsky MR, Atcher RW, Shortkroff S, Lionberger DR, Rose HA, Hurson BJ, Lankenner PA, Anderson RJ, Bloomer WA. Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium 165-ferric hydroxide macroaggregates. Arthritis Rheum 1986;29: 153–159
Sledge CB, Atcher RW, Shortkroff S, Anderson RJ, Bloomer WD, Hurson BJ. Intra-articular radiation synovectomy. Clin Orthop 1984;182:37–40
Gregoir C, Menkes CJ. Rheumatoid elbow: patterns of joint involvement and the outcome of synoviorthesis. Ann Hand Upper Limb Surg 1991;3: 243–246
FernAndez-PalzziF. Radioactivesynoviorthesis in haernophilic haemarthrosis. Rheum Arth Rheumatol 1990;13: 251–260
Onetti CM, Guitiérrez E, Hliba E, Aguirre CR. Synoviorthesis with 32P-colloidal chromic phosphate in rheumatoid atthritis-clinical, histopathologic and arthographic changes. J Rheum 1982;9: 229–238
Rivard GE. Synoviorthesis with radioactive colloids in hemophiliacs. In: Recent advances in hemophilia care. New York: Alan R. Liss; 1990: 215–229
Rivard GE, Girard M, Lamarre C, Jutras M, Danais S, Guay JP, Bé1anger R. Synoviorthesis with colloidal 32P chromic phosphate for hemophilic arthropathy: clinical follow-up. Arch Phys Med Rehabil 1985;66: 753–756
Rivard GE, Girard M, Cliche CL, Guay JP, Bé1anger R, Besner R. Synoviorthesis in patients with hemophilia and inhibitors. Can Med Assoc J 1982;127: 41–42
Ambriz-Fernández R, Rodríguez-Moyado H, Villanueva RM, Muñoz-Olvera R, Gacitua-Zambrano S. Altropatía hemofflica. Enfoques terapéuticos en la clínica de hemofilia. Gac Med Mex 1991;127: 233–240
Ortonowski G, Ziemski JM, Kucharski W, Woy-Wojciechowski J. Synoviorthesis with 198Au colloid gold in haemophilia patients. A preliminary report. Folia Haematol Leipz 1990;4: 505–510
Oliunin IA, Balabanova RM, Drozdovskii BY, Ikonnikov AI. Radioisotope synovectomy in multi-modality treatment of rheumatoid arthritis. Ter Arkh 1989;61: 58–62
Drozdovskii BI, Ikonnikov AI,Krylow VV. Radiosynoviorthese in the treatment of patients with rheumaatoid arthritis. Med Radiol (Mosk) 1990;35: 6–9
Oliunin IA, Manuilova LS. The clinico-morphological assessment of the efficacy of local radiation therapy in rheumatoid arthritis. Ter Arkh 1991;63: 122–125
Fazakas I, Ghegulescu N, Gherman E, Tamas S. Surgical or isotopic synovectomy? Rev Chir (Oftalnaol) 1975;24: 193–198
Merchan ECR, Magallon M, Martin-Villar J, Galindo E, Ortega E, Pardo JA. Long term follow up of haemaphilic arthropathy treated by Au-198 radiation synovectomy. Int Orthop 1993;17: 120–124
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Deutsch, E., Brodack, J.W. & Deutsch, K.F. Radiation synovectomy revisited. Eur J Nucl Med 20, 1113–1127 (1993). https://doi.org/10.1007/BF00173494
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DOI: https://doi.org/10.1007/BF00173494