Preparation and quality control of 177Lu-chitosan for radiosynovectomy

Document Type : Original Article


1 Radiopharmaceutical Research and Development Lab, Nuclear Science and Technology Research Institute, Atomic Energy Organization of Iran (AEOI), Tehran, Iran

2 Radiation Application Group, Faculty of Nuclear Engineering, Shahid Beheshti University, Tehran, Iran


Introduction: Rheumatoid arthritis (RA) is the most common autoimmune disease, leading to the destruction of the joints and causing pain, disability, and immobility in the patients. Radiosynovectomy (RSV) has been applied as an effective treatment for the patients with resistant synovitis after failure of long-term pharmacotherapy and intra-articular steroid injection for more than 50 years. Several radiopharmaceuticals have been developed for RSV so far, but still development of new radiophamaceuticals is of crucial interest. In this research, the 177Lu-chitosan complex (177Lu-CHITO) was introduced as a new agent for RSV.
Methods: 177Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 × 1013 n/cm2·s. 177Lu-CHITO was prepared in the diluted acetic acid solution. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intra-articular injection to rabbits and rats knee joints. The leakage of injected dose from the injection site in the rabbit organs was investigated using SPECT imaging up to 48 hours.
Results: 177Lu was prepared with a specific activity of 2.6-3 and radionuclide purity of 99.98%. 177Lu-CHITO was prepared successfully with high radiochemical purity (95%) and specific activity of 888 TBq/mmol. Both the biodistribution data in rats and SPECT imaging of the rabbit showed that there was no significant leakage of the injected activity even after 192 h.

Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical can be used for effective management of synovial inflammation.


Main Subjects

Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997 Sep;84(3):223-43.
Grossman JM, Brahn E. Rheumatoid arthritis: current clinical and research directions. J Womens Health. 1997 Dec;6(6):627-38.
Schneider P, Farahati J, Reiners C. Radiosynovectomy in rheumatology, orthopedics, and hemophilia. J Nucl Med. 2005 Jan;46 Suppl 1:48S-54S.
Unni PR, Chaudhari PR, Venkatesh M, Ramamoorthy N, Pillai MR. Preparation and bioevaluation of 166Ho labelled hydroxyapatite (HA) particles for radiosynovectomy. Nucl Med Biol. 2002 Feb;29(2):199-209.
Kampen WU, Hellweg L, Massoudi-Nickel S, Czech N, Brenner W, Henze E. Clinical efficacy of radiation synovectomy in digital joint osteoarthritis. Eur J Nucl Med Mol Imaging. 2005 May;32(5):575-80.
Kothari K, Suresh S, Sarma HD, Meera V, Pillai MR. 188Re-labeled hydroxyapatite particles for radiation synovectomy. Appl Radiat Isot. 2003 Apr;58(4):463-8.
Mäkelä O, Penttilä P, Kolehmainen E, Sukura A, Sankari S, Tulamo RM. Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate. Nucl Med Biol. 2002 Jul;29(5):593-8.
Clunie G, Lui D, Cullum I, Edwards JC, Ell PJ. Samarium-153-particulate hydroxyapatite radiation synovectomy: biodistribution data for chronic knee synovitis. J Nucl Med. 1995 Jan;36(1):51-7.
Pirich C, Wanivenhaus A, Graninger W, Kvaternik H, Angelberger P, Pesau B, Havlik E, Flores J, Sinzinger H. Radiosynovectomy with dysprosium-165 iron hydroxide. Acta Med Austriaca. 1993;20(1-2):49-53.
Das T, Pillai MR. Options to meet the future global demand of radionuclides for radionuclide therapy. Nucl Med Biol. 2013 Jan;40(1):23-32.
Chakraborty S, Das T, Banerjee S, Sarma HD, Venkatesh M. Preparation and preliminary biological evaluation of 177Lu-labelled hydroxyapatite as a promising agent for radiation synovectomy of small joints. Nucl Med Commun. 2006 Aug;27(8):661-8.
Chakraborty S, Das T, Sarma HD, Venkatesh M, Banerjee S. Preparation and preliminary studies on 177Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer. Nucl Med Biol. 2008 Jul;35(5):589-97.
Brodack JW, Chinen LK, Deutsch E, Deutsch KF. Studies on radiolabelling of hydroxyapatite particles for use as radiation synovectomy agents. J Nucl Med. 1992;33:980.
Harish Prashanth KV, Tharanathan RN. Chitin/chitosan: modifications and their unlimited application potential—an overview. Trends Food Sci Tech. 2007;18:117–31.
Rinaudo M. Chitin and chitosan: Properties and applications. Prog Polym Sci. 2006;31(7):603–32.
Suzuki YS, Momose Y, Higashi N, Shigematsu A, Park KB, Kim YM, Kim JR, Ryu JM. Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice. J Nucl Med. 1998 Dec;39(12):2161-6.
Shin BC, Park KB, Jang BS, Lim SM, Shim CK. Preparation of 153Sm-chitosan complex for radiation synovectomy. Nucl Med Biol. 2001 Aug;28(6):719-25.
Industrial Applications and Chemistry Section, International Atomic Energy Agency. Manual for reactor produced radioisotopes. Vienna: IAEA; 2003.  
Chakraborty S, Das T, Banerjee S, Subramanian S, Sarma HD, Venkatesh M. 175Yb-labeled hydroxyapatite: a potential agent for use in radiation synovectomy of small joints. Nucl Med Biol. 2006 May;33(4):585-91.
Sledge CB, Noble J, Hnatowich DJ, Kramer R, Shortkroff S. Experimental radiation synovectomy by 165Dy ferric hydroxide macroaggregate. Arthritis Rheum. 1977 Sep-Oct;20(7):1334-42.
Davis MA, Chinol M. Chinol M. Radiopharmaceuticals for radiation synovectomy: evaluation of two yttrium-90 particulate agents. J Nucl Med. 1989 Jun;30(6):1047-55.
Johnson LS, Yanch JC, Shortkroff S, Barnes CL, Spitzer AI, Sledge CB. Beta-particle dosimetry in radiation synovectomy. Eur J Nucl Med. 1995 Sep;22(9):977-88.
Boussina I, Toussaint M, Ott H, Hermans P, Fallet GH. A double-blind study of erbium169 synoviorthesis in rheumatoid digital joints. Results after one year. Scand J Rheumatol. 1979;8(2):71-4.
Kahan A, Mödder G, Menkes CJ, Verrier P, Devaux JY, Bonmartin A, De Rycke Y, Manil L, Chossat F, Tebib J. 169Erbium-citrate synoviorthesis after failure of local corticosteroid injections to treat rheumatoid arthritis-affected finger joints. Clin Exp Rheumatol. 2004 Nov-Dec;22(6):722-6.
Gratz S, Göbel D, Behr TM, Herrmann A, Becker W. Correlation between radiation dose, synovial thickness, and efficacy of radiosynoviorthesis. J Rheumatol. 1999 Jun;26(6):1242-9.
Clunie G, Fischer M; EANM. EANM procedure guidelines for radiosynovectomy. Eur J Nucl Med Mol Imaging. 2003 Mar;30(3):BP12-6.
Prabhakar G, Sachdev SS, Umamaheswari S, Sivaprasad N, Bhatia MH, Chaudhari PR, Solav SV. et al. Development of samarium [32P] phosphate colloid for radiosynoviorthesis applications: preparation, biological and preliminary clinical studies experience. Appl Radiat Isot. 2007 Dec;65(12):1309-13.