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The preparation of 165Dy-labeled chitosan for radiosynovectomy applications is described in this paper. 165Dy (T1/2 = 2.33 h) was prepared by irradiation of natural Dy(NO3)3 at a flux of 3.4 x 1013 neutrons/cm2.s for about 6 h. The irradiation resulted in the production of 11.1 GBq (300 mCi) of 165Dy activity. Emitting gamma ray (94.7 keV) and beta particles (Emax = 1.3 MeV, 83%) 165Dy decays to 165Ho. Eight hours after bombardment, the corresponding specific activity was 703 MBq/mg (19 mCi/mg). The irradiated target was dissolved in 0.1 N HCl solution. Radionuclidic purity was ascertained by high resolution gamma spectrometry. Chitosan solution was prepared in acetic acid solution (pH 3). The chitosan solution was labeled with 165Dy to prepare 165Dy-chitosan (165Dy-Chit) complex (labeling yield, greater than 99% and specific activity small tilde 3.7 TBq/mmol). In optimized conditions (pH 3, 35 mg/4 ml chitosan acidic solution, and 370 MBq of 165Dy) Chit was stable after 48 h. Bioevaluation of the prepared 165Dy-Chit was carried out by injecting 37 MBq (1 mCi, 50.100 mi1) directly into the knee joints of wild rats. Free 165Dy cation was also injected to study the effect of complex formation on the retention of radionuclide in the administered site. To study the consequence of radioactivity leakage from the administration site, a dilute sample of the complex was injected intravenously into the rats followed by biodistribution studies. It was observed that there was no significant extra-articular leakage of the injected activity over the study period of 24 h post-injection.
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277--282
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Bibliogr. 19 poz., rys.
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- Radiopharmaceutical Research and Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), 14155-1339, Tehran, Iran, Tel.: +98 21 8822 1117, Fax: +98 21 8822 1116, smshirvani@aeoi.org.ir
Bibliografia
- 1. Ansell BM, Cook A, Mallard JR, Bywaters EGL (1963) Evaluation of intraarticular colloidal gold Au-198 in the treatment of persistent knee effusions. Ann Rheum Dis 22:435–439
- 2. Bae KP, Mi YK, Rok JI (1996) Radioactive chitosan complex and its macroaggregates for use in internal radiation therapy and their preparation method. European Patent Application EP0730870, Patent no. 5762903
- 3. Johnson LS, Yanch JC, Shortkroff S, Barnes CL, Sitzer AI, Sledze CB (1995) Beta-particle dosimetry in radiation synovectomy. Eur J Nucl Med 22:97–988
- 4. Kampen WU, Brenner W, Czech N, Henze E (2002) Intraarticular application of unsealed beta-emitting radionuclides in the treatment course of inflammatory joint diseases. Curr Med Chem – Anti-Inflammatory & Anti-Allergy Agents 1:77–87
- 5. Kubota N (1993) Molecular weight dependence of the properties of chitosan and chitosan hydrogel for use in sustained release drug. Bull Chem Soc Jpn 66:1807–1812
- 6. Kwak C, Hong SK, Seong SK, Ryu JM, Park MS, Lee SE (2001) Effective local control of prostate cancer by intratumoral injection of 166Ho-chitosan complex (DW-166HC) in rats. Nucl Med Biol 28:719–725
- 7. Lee SH, Suh JS, Kim HS, Lee JD, Song J, Lee SK (2003) MR evaluation of radiation synovectomy of the knee by means of intra-articular injection of holmium-166-chitosan complex in patients with rheumatoid arthritis: results at 4-month follow-up. Korean J Radiol 4;3:170–178
- 8. Mäkelä O, Penttilä P, Kolehmainen E, Sukura A, Sankari S, Tulamo RM (2002) Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate. Nucl Med Biol 29:593–598
- 9. Neves M, Waerenborgh F, Patrioci L (1987) 109Palladium and 166Holmium potential radionuclides for synoviotherapy-radiation absorbed dose calculations. Appl Radiat Isot 38:745–749
- 10. Oka M, Rekonen A, Rvotsi A, Seppala O (1971) Intraarticular injection of Y-90-resin colloid in the treatment of rheumatoid knee joint effusions. Acta Rheumatol Scand 17:148–160
- 11. Pinch C, Pilger A, Schwameis E et al. (2000) Radiation synovectomy using 165Dy ferric-hydroxide and oxidative DNA damage in patients with different types of arthritis. Nucl Med 41:250–256
- 12. Ravi Kumar MNV, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb AJ (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 104:6017–6084
- 13. Shin BC, Park KB, Jang BS, Lim SM, Shim CK (2001)Preparation of 153Sm-chitosan complex for radiation synovectomy. Nucl Med Biol 28;6:719–725
- 14. Sledze CB (1979) Correction of arthritic deformities in the lower extremities and spine. In: McCarty (ed) Arthritis and allied conditions, 9th ed. Lea and Febiger, Philadelphia, pp 1276–1299
- 15. Sledze CB, Noble J, Hnatowich DJ, Kramer R, Shortkroff S (1977) Experimental radiation synovectomy by 165Dy ferric hydroxide macroaggregate. Arthritis Rhenum-US 20:1334–1342
- 16. Sledze CB, Zuckerman JD, Zalutsky MR et al. (1986) Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium-165 ferric hydroxide macroaggregates. Arthritis Rhenum-US 69:153–159
- 17. Song J, Suh CH, Park YB et al. (2001) A phase I/II study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis. Eur J Nucl Med 28;4:489–497
- 18. Virkkunen M, Krusius FE, Heiskanen T (1967) Experiences of intra-articular administration of radioactive gold. Acta Rheumatol Scand 13:81–91
- 19. Von Reis G, Swensson A (1951) Intraarticular injection of acid osmic in painful joint effusions. Acta Med Scand 259:27–32
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Bibliografia
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bwmeta1.element.baztech-article-BUJ8-0007-0015