Development and assessment of 153Sm-zoledronate complex as a possible bone pain palliative agent

Document Type : Original Article


1 Department of Inorganic Chemistry, University of Mazandaran, Babolsar, Iran

2 Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran

3 Radioisotope Products and Radiation Technology Section, Department of Nuclear Sciences and Applications, International Atomic Energy Agency (IAEA), Vienna, Austria


Introduction:In this work, 153Sm-zoledronate (153Sm-ZLD) was studied using computational chemistry methods and prepared for possible use in bone pain palliation therapy.
Methods: The Sm(ZLD)2.7H2O complex was synthesized and characterized in solid state using computational chemistry methods followed by 153Sm-ZLD complex production, stablity, hydroxyapatite (HA) tests and also biodictribution studies in animals were studied and used for absorbed dose determination in critical organs.
Results: The Sm(ZLD)2.7H2O complex was synthesized and characterized in solid state and computational chemistry methods showed that 1:1, 1:2 and 1:3 complex formation are possible in aqueous solution. 153Sm-ZLD complex was prepared with >99% radiochemical purity (ITLC, HPLC) and specific activity of 4.4 GBq/mmol. It was stable for 24h with >95% binding to HA with accumulation in rat bones and kidneys. Absorbed dose showed kidney and osteogenic tissue as critical organs.

Conclusion: The 153Sm-ZLD complex data were compared to 153Sm-EDTMP and 153Sm-BPAMD.


Main Subjects

  1. Palma E, Correia JD, Campello MP, Santos I. Bisphosphonates as radionuclide carriers for imaging or systemic therapy. Mol Biosyst. 2011 Nov;7(11):2950-66.
  2. Fleisch H, Russell RG, Francis MD. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science. 1969 Sep 19;165(3899):1262-4.
  3. Majkowska A, Neves M, Antunes I, Bilewicz A. Complexes of low energy beta emitters 47Sc and 177Lu with zoledronic acid for bone pain therapy. Appl Radiat Isot. 2009 Jan;67(1):11-3..
  4.  Abruzzese E, Iuliano F, Trawinska MM, Di Maio M.153Sm: its use in multiple myeloma and report of a clinical experience. Expert Opin Investig Drugs. 2008 Sep;17(9):1379-87.
  5. D'angelo G, Sciuto R, Salvatori M, Sperduti I, Mantini G, Maini CL, Mariani G. Targeted "bone-seeking" radiopharmaceuticals for palliative treatment of bone metastases: a systematic review and meta-analysis. Q J Nucl Med Mol Imaging. 2012 Dec;56(6):538-43.
  6.  Simón J, Frank RK, Crump DK, Erwin WD, Ueno NT, Wendt RE 3rd. A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical. Nucl Med Biol. 2012 Aug;39(6):770-6.
  7. Astrand J, Aspenberg P. Topical, single dose bisphosphonate treatment reduced bone resorption in a rat model for prosthetic loosening. J Orthop Res. 2004 Mar;22(2):244-9.
  8. (viewed Nov. 23, 2015)
  9. Asikoglu M, Durak FG. The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m. Appl Radiat Isot. 2009 Sep;67(9):1616-21.
  10. Qiu L , Lin J, Cheng W, Wang Y, Luo S. 99mTc-labeled butyl-substituted zoledronic acid as a novel potential SPECT imaging agent: preparation and preclinical pharmacology study. Med Chem Res. 2013;22(12):6154-6162.
  11. Nikzad M, Jalilian AR, Shirvani-Arani S, Bahrami-Samani A, Golchoubian H. Production, quality control and pharmacokinetic studies of 177Lu-Zoledronate for bone pain palliation therapy. J Radioanal Nucl Chem. 2013;298:1273–1281.
  12. Arabieh M. Khodabandeh MH, Karimi-Jafari MH, Platas-Iglesias C. Zare K. Complexation of Sm3+ and pamidronate: A DFT study. J Rare Earths. 2015;33(3):310–319.
  13.  Dutra JD1, Filho MA, Rocha GB, Freire RO, Simas AM, Stewart JJ. Sparkle/PM7 Lanthanide Parameters for the Modeling of Complexes and Materials. J Chem Theory Comput. 2013 Aug 13;9(8):3333-3341.
  14. International Atomic Energy Agency. Manual for reactor produced radioisotopes. Vienna: IAEA; 2003. p.189-192.
  15.  Neves M, Gano L, Pereira N, Costa MC, Costa MR, Chandia M, Rosado M, Fausto R. Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies. Nucl Med Biol. 2002 Apr;29(3):329-38.
  16.  OLINDA - Organ Level Internal Dose Assessment Code (Version 1.1), 2007. copyright Vanderbilt University.
  17.  Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose. Sixth International Radiopharmaceutical Dosimetry Symposium. Oak Ridge, TN: Oak Ridge Associated Universities; 1996. p. 705-16.
  18. Qiu L, Lin J, Wang L, Cheng W, Cao Y, Liu X, Luo S. A Series of imidazolyl-containing bisphosphonates with abundant hydrogen-bonding interactions: syntheses, structures, and bone-binding affinity. Aust J Chem. 2014;67(2):192-205.
  19.  Cao DK, Li YZ, Zheng LM. Layered cobalt(II) and nickel(II) diphosphonates showing canted antiferromagnetism and slow relaxation behavior. Inorg Chem. 2007 Sep 3;46(18):7571-8.
  20.  Cao DK, Liu MJ, Huang J, Bao SS, Zheng LM.Cobalt and manganese diphosphonates with one-, two-, and three-dimensional structures and field-induced magnetic transitions. Inorg Chem. 2011 Mar 21;50(6):2278-87.
  21.  Naseri Z, Hakimi A, Jalilian AR, Shirvani-Arani S, Bahrami-Samani A, Ghannadi-Maragheh M. Synthesis, quality control and biological evaluation of tris[(1,10-phenanthroline)[153Sm]samarium(III)]trithiocyanate complex as a therapeutic agent. Radiochim Acta. 2012;100(4):267-272.
  22. Verhulst A, Sun S, McKenna CE, D'Haese PC. Endocytotic uptake of zoledronic acid by tubular cells may explain its renal effects in cancer patients receiving high doses of the compound. PLoS One. 2015 Mar 10;10(3):e0121861.
  23. Bahrami-Samani A, Ghannadi-Maragheh M, Jalilian AR, Meftahi M, Shirvani-Arani S, Moradkhani S. Production, quality control and biological evaluation of 153Sm-EDTMP in wild-type rodents. Iran J Nucl Med. 2009;17(2):12-19
  24.  Rabie A, Enayati R, Yousefnia H, Jalilian AR, Shamsaei M, Zolghadri S, Bahrami-Samani A, Hosntalab M. Preparation, quality control and biodistribution assessment of ¹⁵³Sm-BPAMD as a novel agent for bone pain palliation therapy. Ann Nucl Med. 2015 Dec;29(10):870-6.
  25. Talwer GP, Srivastava LM. Textbook of biochemistry and human biology. August 2004 Verlag: Prentice-Hall of India Pvt. Ltd. 2004.