Preclinical studies of 166Ho-chitosan for treatment of hepatocellular carcinoma

Document Type : Original Article


1 Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

2 Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

3 Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

4 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran


Introduction: Recently, due to the special characteristics of 166Ho and chitosan, 166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use. Methods:In this study, 166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit`s liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours. Results:Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection. Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method.


Main Subjects

Sundram F. Radionuclide therapy of hepatocellular carcinoma. Biomed Imaging Interv J. 2006 Jul;2(3):e40. 
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429-42.
Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9.
Lau WY, Leung WT, Ho S, Leung NW, Chan M, Lin J, Metreweli C, Johnson P, Li AK. Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer. 1994 Nov;70(5):994-9.
Raoul JL, Guyader D, Bretagne JF, Heautot JF, Duvauferrier R, Bourguet P, Bekhechi D, Deugnier YM, Gosselin M. Prospective randomized trial of chemoembolization versus intra-arterial injection of 131I-labeled-iodized oil in the treatment of hepatocellular carcinoma. Hepatology. 1997 Nov;26(5):1156-61.
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.
Huh R, Park YS, Lee JD, Chung YS, Park YG, Chung SS, Chang JW.Therapeutic effects of Holmium-166 chitosan complex in rat brain tumor model. Yonsei Med J. 2005 Feb 28;46(1):51-60.
Seong SK, Ryu JM, Shin DH, Bae EJ, Shigematsu A, Hatori Y, Nishigaki J, Kwak C, Lee SE, Park KB. Biodistribution and excretion of radioactivity after the administration of 166Ho-chitosan complex (DW-166HC) into the prostate of rat. Eur J Nucl Med Mol Imaging. 2005 Aug;32(8):910-7.
Zolghadri S, Jalilian AR, Yousefnia H, Bahrami-Samani A, Shirvani-Arani S, Mazidi M, Akhlaghi M, Ghannadi-Maragheh M. Production and quality control of 166Ho-Chitosan for therapeutic applications. Iran J Nucl Med. 2010;18(2):1-8.
Kim JK, Han KH, Lee JT, Chon CY, Moon YM, Paik YH. The long term therapeutic efficacy and the safety of percutaneous holmium injection for the treatment of small hepatocellular carcinoma. J Hepatol. 2003;38(suppl 2):6.
Sohn JH, Choi HJ, Lee JT, Lee JD, Kim JH, Moon YM, Park K, Park KB, Kim E, Yoo NC. Phase II study of transarterial holmium-166-chitosan complex treatment in patients with a single, large hepatocellular carcinoma. Oncology. 2009;76(1):1-9.
Sgouros G, Hobbs RF, Abou DS. The role of preclinical models in radiopharmaceutical therapy. Am Soc Clin Oncol Educ Book. 2014:e121-5.
International Atomic Energy Agency. Manual for reactor produced radioisotopes, IAEA-TECDOC-1340. Vienna: IAEA; 2003. p.71-74.
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.