Development of 153Sm/177Lu-EDTMP as a possible therapeutic complex

Document Type : Original Article

Authors

1 Radiopharmaceutical Research and Development Lab (RRDL), Nuclear Science and Technology Research Institute (NSTRI), P.O. Box 14395-836, Tehran, Iran

2 Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Introduction:Targeted radionuclide therapy (TRT) has been demonstrated to be an effective therapeutic tool in patients with disseminated bone metastasis. TRT is generally performed with a single radionuclide. In this study we investigated the feasibility of combined TRT with a high-energy beta emitter (153Sm) and a low energy beta emitter (177Lu) in wistar rats.
Methods: The cocktail complex of 153Sm/177Lu-EDTMP was prepared. To determine the effect of metal-to-ligand (Me:EDTMP) molar ratio on labeling yield, several complex were analyzed after changing Me:EDTMP molar ratio from 1:1 to 1:50. 153Sm/177Lu-EDTMP was administered intravenously through the tail vein of wistar rats. Biodistribution data were collected at 2 hours to 7 day post injection and scintigraphic images were taken at 24 hours and 1, 2 week after administration of radiopharmaceutical.
Results: The results revealed high skeletal uptake (3.5% and 3.4% ID/g at 24 hours post injection for 153Sm and 177Lu, respectively) with rapid blood clearance and minimal uptake in any of the major organs. Scintigraphic images verified high skeletal uptake.

Conclusion: Our results indicate that the combination of 153Sm and 177Lu is feasible and safe. This study suggests that the combination of different radionuclides with different radiation energies and half-life, such as 153Sm and 177Lu, could be advantageous in patients with tumoral lesions of different sizes.

Keywords

Main Subjects

References

  1. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12.
  2. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004 Apr 15;350(16):1655-64.
  3. Lipton A. Implications of bone metastases and the benefits of bone-targeted therapy. Semin Oncol. 2010 Oct;37 Suppl 2:S15-29.
  4. Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009 Apr 1;27(10):1564-71.
  5. Pandit-Taskar N, Larson SM, Carrasquillo JA. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride. J Nucl Med. 2014 Feb;55(2):268-74.
  6. Ayati N, Aryana K, Jalilian A, Hoseinnejad T, Samani AB, Ayati Z, Shariati F, Zakavi SR. Treatment efficacy of (153)Sm-EDTMP for painful bone metastasis. Asia Ocean J Nucl Med Biol. 2013 Spring;1(1):27-31.
  7. Pirayesh E, Amoui M, Mirzaee HR, Tabei F, Rakhsha A, Kalantari BA, Shafiei B, Assadi M, Asli IN. Phase 2 study of a high dose of 186Re-HEDP for bone pain palliation in patients with widespread skeletal metastases. J Nucl Med Technol. 2013 Sep;41(3):192-6.
  8. Rubini G1, Nicoletti A, Rubini D, Asabella AN. Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium. Cancer. Cancer Biother Radiopharm. 2014 Feb;29(1):1-11.
  9. Sartor O, Reid RH, Bushnell DL, Quick DP, Ell PJ. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer. 2007 Feb 1;109(3):637-43.
  10. Kuroda I. Strontium-89 for prostate cancer with bone metastases: the potential of cancer control and improvement of overall survival. Ann Nucl Med. 2014 Jan;28(1):11-6.
  11. Iakovou I, Doumas A, Badiavas K, Mpalaris V, Frangos S, Farmakis G. Pain palliative therapy in women with breast cancer osseous metastatic disease and the role of specific serum cytokines as prognostic factors. Cancer Biother Radiopharm. 2014 Apr;29(3):116-23.
  12. Pacilio M, Ventroni G, Basile C, Ialongo P, Becci D, Mango L. Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with 153Sm-EDTMP. Eur J Nucl Med Mol Imaging. 2014 Feb;41(2):238-52.
  13. Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin Nucl Med. 2010 Mar;40(2):89-104.
  14. Biersack HJ, Palmedo H, Andris A, Rogenhofer S, Knapp FF, Guhlke S, Ezziddin S, Bucerius J, von Mallek D. Palliation and survival after repeated (188)Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. J Nucl Med. 2011 Nov;52(11):1721-6.
  15. Ferreira S, Dormehl I, Botelho MF. Radiopharmaceuticals for bone metastasis therapy and beyond: a voyage from the past to the present and a look to the future. Cancer. Cancer Biother Radiopharm. 2012 Nov;27(9):535-51.
  16. Ando A, Ando I, Tonami N, Kinuya S, Kazuma K, Kataiwa A, Nakagawa M, Fujita N. 177Lu-EDTMP: a potential therapeutic bone agent. Nucl Med Commun. 1998 Jun;19(6):587-91.
  17. Láznícek M, Láznícková A, Budský F, Prokop J, Kopicka K. Comparison of biological characteristics of EDTMP complexes with 99mTc, 111In and 153Sm in rats. Appl Radiat Isot. 1994 Sep;45(9):949-53.
  18. Beiki D, Haddad P, Fallahi B, Keyvan A, Gholamrezanezhad A, Mirzaei H, Saghari M, Amouzegar-Hashemi F, Kazemian A, Fard-Esfahani A, Eftekhari M. Effectiveness and complications of 153Sm-EDTMP in palliative treatment of diffuse skeletal metastases. Iran J Nucl Med. 2013;21(1):26-32.
  19. Chakraborty S, Das T, Banerjee S, Balogh L, Chaudhari PR, Sarma HD, Polyák A, Máthé D, Venkatesh M, Janoki G, Pillai MR. 177Lu-EDTMP: a viable bone pain palliative in skeletal metastasis. Cancer. Cancer Biother Radiopharm. 2008 Apr;23(2):202-13.
  20. Shinto AS, Shibu D, Kamaleshwaran KK, Das T, Chakraborty S, Banerjee S, Thirumalaisamy P, Das P, Veersekar G. ¹⁷⁷Lu-EDTMP for treatment of bone pain in patients with disseminated skeletal metastases. J Nucl Med Technol. 2014 Mar;42(1):55-61.
  21. Yuan J, Liu C, Liu X, Wang Y, Kuai D, Zhang G, Zaknun JJ. Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study. Clin Nucl Med. 2013 Feb;38(2):88-92.
  22. Collins C, Eary JF, Donaldson G, Vernon C, Bush NE, Petersdorf S, Livingston RB, Gordon EE, Chapman CR, Appelbaum FR. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J Nucl Med. 1993 Nov;34(11):1839-44.
  23. Ranjbar H, Ghannadi-Maragheh M, Bahrami-Samani A, Beiki D. Dosimetric evaluation of 153Sm-EDTMP, 177Lu-EDTMP and 166Ho-EDTMP for systemic radiation therapy: Influence of type and energy of radiation and half-life of radionuclides. Radiat Phys Chem. 2015;108:60-64.
  24. Ranjbar H, Bahrami-Samani A, Beiki D, Shirvani-Arani S, Ghannadi-Maragheh M. Evaluation of Evaluation of 153Sm/177Lu-EDTMP mixture in wild-type rodents as a novel combined palliative treatment of bone pain agent. J Radioanal Nucl Chem. 2015;303(1):71–79.

Files

Share

How to cite

Statistics