DA-7911, $^{188}Rhenium-tin$ Colloid, as a New Therapeutic Agent of Rheumatoid Arthritis

  • Shin, Chang-Yell (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Son, Miwon (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Ko, Jun-Il (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Jung, Mi-Young (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Lee, In-Ki (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Kim, Soon-Hoe (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Kim, Won-Bae (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Jeong, Jae-Min (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Song, Yeong-Wook (Department of Internal Medicine, College of Medicine, Seoul National University)
  • 발행 : 2003.02.01

초록

Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

키워드

참고문헌

  1. Davis, M. A. and Chinol, M., Radiopharmaceuticals for radiation D. K. Kim et al. synovectomy: evaluation of two yttrium-90 particulate agents. J. Nucl. Med., 30, 1047-1055 (1989)
  2. Feldmann, M., Brennan, F. M., and Maini, R. N., Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol., 14, 397-440 (1996) https://doi.org/10.1146/annurev.immunol.14.1.397
  3. Jeong, J. M., Lee, Y. J., Kim, Y. J., Chang, Y. S., Lee, D. S., Chung, J. K., Song, Y W, and Lee, M. C., Preparation of rhenium188-tin colloid as a radiation synovectomy agent and comparison with rhenium-188-sulfur colloid. Appl. Radiat. Isot., 52, 851-855 (2000) https://doi.org/10.1016/S0969-8043(99)00131-1
  4. Johnson, L. S., Yanch, J. C., Shortkroff, S., Barnes, C. L., Spitzer, A. I., and Sledge, C. B., Beta-particle dosimetry in radiation synovectomy. Eur. J. Nucl. Med., 22, 977-988 (1995) https://doi.org/10.1007/BF00808408
  5. Jorgensen, C. and Gay, S., Gene therapy in osteoarticular diseases: where are we? Immunol. Today, 19, 387-391 (1998) https://doi.org/10.1016/S0167-5699(98)01296-1
  6. Kim, Y. J., Jeong, J. M., Chang, Y. S., Lee, Y. J., Lee, D. S., Chung, J. -K., Lee, M. C., and Song, Y. W., Preparation and biodistribution of Re-188 sulfur colloid. Korean J. Nucl. Med., 32, 298-304 (1998)
  7. Knapp, F. F., Jr., Mirzadeh, S., Beets, A. L., O'Doherty, M., Blower, P. J., Verdera, E. S., Gaudiano, J. S., Kropp, J., Guhlke, J., Palmedo, H., and Biersack, H. J., Reactor-produced radioisotopes from ORNL for bone pain palliation. Appl. Radiat. Isot., 49, 309-315 (1998) https://doi.org/10.1016/S0969-8043(97)00043-2
  8. Pettipher, E. R., Henderson, B., Hardingham, T., and Ratcliffe, A., Cartilage proteoglycan depletion in acute and chronic antigen-induced arthritis. Arthritis Rheum., 32, 601-607 (1989) https://doi.org/10.1002/anr.1780320514
  9. Ures, M., Savio, E., Malanga, A., Femandez, M., Paolino, A., and Gaudiano, J., Physico-chemical characterisation and biological evaluation of 188-Rhenium colloids for radiosynovectomy. BMC Nucl. Med., 2, 1 (2002) https://doi.org/10.1186/1471-2385-2-1
  10. Wang, S. J., Lin, W. Y., Chen, M. N., Chen, J. T., Ho, W. L., Hsieh, B. T., Huang, H., Shen, L. H., Ting, G., and Knapp, F. F., Jr. Histologic study of effects of radiation synovectomy with Rhenium-188 microsphere. Nucl. Med. Biol., 28, 727-732 (2001) https://doi.org/10.1016/S0969-8051(01)00228-1
  11. Wang, S. J., Lin, W. Y., Hsieh, B. T., Shen, L. H., Tsai, Z. T., Ting, G., and Knapp, F. F., Jr. Rhenium-188 sulphur colloid as a radiation synovectomy agent. Eur. J. Nucl. Med., 22, 505-507 (1995) https://doi.org/10.1007/BF00817272
  12. Zuckerman, J. D., Sledge, C. B., Shortkroff, S., and Venkatesan, P., Treatment of rheumatoid arthritis using radiopharmaceuticals. Int. J. Rad. Appl. Instrum. B., 14, 211-218 (1987) https://doi.org/10.1016/0883-2897(87)90044-4