Preparation and biological evaluation of 186/188Re-HEDP as a new cocktail radiopharmaceutical for palliative treatment of osseous metastases in wild type rat

Document Type : Original Article

Authors

1 Department of Physics, Payame Noor University, Tehran, Iran

2 Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

3 Pars Isotope Company, Therapeutic Radiopharmaceuticals Department, Tehran, Iran

Abstract

Introduction: The palliative care in patients with bone metastasis includes variety of techniques such as conventional analgesics, surgery, external beam radiotherapy, hormone therapy, chemotherapy and using bone-seeking radiopharmaceuticals. Even some of the recent works used combined methods like chemotherapy and radionuclide therapy or using radionuclide therapy as adjuvant to external beam therapy or even using tandem 2 separate radiopharmaceuticals. In line with combined methods, due to the improved efficacy of two radioisotopes with complementary properties in treatment, in this study we proposed using compositional radiopharmaceuticals as a new idea. In this study as a new idea the combined radionuclide therapy have been investigated with utilizing 188Re and 186Re complementary features in the 188/186Re-HEDP cocktail to achieve the maximum efficacy.
Methods: 186Re and 188Re have been produced simultaneously with identical activities by natural rhenium irradiation. Produced 188/186Re-HEDP with high radiochemical purity was administered intravenously to rats. Biodistribution data were collected at 2, 4, 24, 48 and 72 hours post injection and scintigraphic images were taken at 24 hours after administration of radiopharmaceutical.
Results: 188/186Re-HEDP was prepared with radiochemical purity of nearly 99%. Its biodistribution data showed high uptake and durability in the skeletal tissues without significant uptake in other major organs.
Conclusion: The study results demonstrate that the combination of 186Re and 188Re in cocktail radiopharmaceutical form is achievable and safe. The complementary features of 188Re and 186Re, due to their different energies, half-lives and penetration ranges can lead to more efficacy in bone metastases treatment.

Keywords

Main Subjects

References

  1. Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, Goncalves F. Bone metastases: an overview. Oncol Rev. 2017 May 9;11(1):321.
  2. Cecchini M, Wetterwald A, van der Pluijm G, Thalmann G. Molecular and biological mechanisms of bone metastasis. EAU Update Series. 2005;3(4):214-226.
  3. Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 2004 Aug;45(8):1358-65.
  4. Sartor O. Overview of samarium sm 153 lexidronam in the treatment of painful metastatic bone disease. Rev Urol. 2004;6(Suppl 10):S3-S12.
  5. Bodei L, Lam M, Chiesa C, Flux G, Brans B, Chiti A, Giammarile F; European Association of Nuclear Medicine (EANM). EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging. 2008 Oct;35(10):1934-40.
  6. Lee KS, Chung BH. Radiopharmaceutical therapy in metastatic CRPC. In: Kim CS. Management of advanced prostate cancer. Springer; 2018. p. 175-179.
  7. Lange R, Overbeek F, de Klerk JM, Pasker-de Jong PC, van den Berk AM, Ter Heine R, Rodenburg CJ, Kooistra A, Hendrikse NH, Bloemendal HJ. Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Nuklearmedizin. 2016 Sep 26;55(5):188-95.
  8. Handkiewicz-Junak D, Poeppel TD, Bodei L, Aktolun C, Ezziddin S, Giammarile F, Delgado-Bolton  RC, Gabriel M. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging. 2018 May;45(5):846-859.
  9. Maxon H, Deutsch E, Thomas S, Libson K, Lukes S, Williams C, Ali S. Re-186 (Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies. Radiology. 1988 Feb;166(2):501-7.
  10. Maxon 3rd HR, Schroder LE, Thomas SR, Hertzberg VS, Deutsch EA, Scher HI. Re-186 (Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology. 1990 Jul;176(1):155-9.
  11. Bai HS, Jin XH, Wang F, Du J, Liu Y, Chen D. Preparation of a cold kit of 186Re (Sn)-HEDP. J Radioanal Nucl Chem. 1996;206(1):43-50.
  12. Kothari K, Pillai MR, Unni PR, Shimpi HH, Noronha OP, Samuel AM. Preparation, stability studies and pharmacological behavior of [186Re] Re–HEDP1. Appl Radiat Isot. 1999 Jul;51(1):51-8.
  13. Bagatti D, Cantone MC, Giussani A, Ridone S, Birattari C, Bonardi M, Groppi F, Martinotti A, Morzenti S, Gallorini M, Rizzio E. Analytical and radioanalytical quality control of purity and stability of radiopharmaceutical compound [186gRe] Re-HEDP for bone metastases pain palliation. J Radioanal Nucl Chem. 2005;263(2):515-520.
  14. Ridone S, Bonardi M, Groppi F, Martinotti A, Alfassi Z. Paper radiochromatography for evaluation of radiochemical purity and stability of [186gRe] Re-HEDP in biological samples after human administration. J Radioanal Nucl Chem. 2008;277(1):117-123.
  15. Denis-Bacelar AM, Chittenden SJ, Dearnaley DP, Divoli A, O’Sullivan JM, McCready VR, Johnson B, Du  Y, Flux GD.   Phase I/II trials of 186 Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival. Eur J Nucl Med Mol Imaging. 2017 Apr;44(4):620-629.
  16. Denis-Bacelar AM, Chittenden SJ, McCready VR, Divoli A, Dearnaley DP, O’Sullivan JM, Johnson B, Flux GD. Bone lesion absorbed dose profiles in patients with metastatic prostate cancer treated with molecular radiotherapy. Br J Radiol. 2018 Apr;91(1084):20170795.
  17. Pirayesh E, Amoui M, Mirzaee HR, Tabei F, Rakhsha A, Kalantari BA, Shafiei B, Assadi M, Neshandar Asli I. 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.
  18. van Dodewaard-de Jong JM, de Klerk JMH, Bloemendal HJ, van Bezooijen BP, de Haas MJ, Wilson RH, O'Sullivan JM. A phase I study of combined docetaxel and repeated high activity 186 Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial). Eur J Nucl Med Mol Imaging. 2011 Nov;38(11):1990-8.
  19. Maxon 3rd HR, Schroder LE, Washburn LC, Thomas SR, Samaratunga RC, Biniakiewicz D, Moulton JS, Cummings D., Ehrhardt GJ, Morris V. Rhenium-188 (Sn) HEDP for treatment of osseous metastases. J Nucl Med. 1998 Apr;39(4):659-63.
  20. Beiki D, Tajik M, Haddad P, Fallahi B, Arefpour AM, Mirzaei H, Fard-Esfahani A, Emami-Ardekani A,  Eftekhari M. Effectiveness and complications of 188Re-HEDP in palliative treatment of diffuse skeletal metastases. Iran J Nucl Med. 2015;23(1):44-48.
  21. Orsini F, Guidoccio F, Mazzarri S, Mariani G. Palliation and survival after repeated 188Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. J Nucl Med. 2012 Aug;53(8):1330-1; author reply 1332.
  22. Liepe K. 188Re-HEDP therapy in the therapy of painful bone metastases. World J Nucl Med. 2018;17(3):133-138.
  23. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer. 2003 Aug 18;89(4):625-9.
  24. Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G, Risse J, Grünwald F, Knapp Jr FF, Biersack HJ. Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med. 2000 Feb;27(2):123-30.
  25. Zhang H, Tian M, Li S, Liu J, Tanada S, Endo K. Rhenium-188-HEDP therapy for the palliation of pain due to osseous metastases in lung cancer patients. Cancer Biother Radiopharm. 2003 Oct;18(5):719-26.
  26. Kumar C, Sharma R, Vats K, Mallia MB, Das T, Sarma HD, Dash A. Comparison of the efficacy of 177 Lu-EDTMP, 177 Lu-DOTMP and 188 Re-HEDP towards bone osteosarcoma: an in vitro study. J Radioanal Nucl Chem. 2019;319(1):51-59.
  27. Ramakurup REK, Chirayil V, Pandiyan A, Mallia MB, Kameswaran M, Shinto A, Dash A. Rhenium-188 hydroxyethane 1, 1-diphosphonic acid (HEDP) for bone pain palliation using BARC-HEDP kits versus Pars-HEDP kits: A comparison on preparation and performance aspects at hospital radiopharmacy. Indian J Nucl Med. Oct-Dec 2018;33(4):302-305.
  28. Ranjbar H, Bahrami-Samani A, Beiki D, Shirvani-Arani S, Ghannadi-Maragheh M. 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.
  29. Alavi M, Khajeh-Rahimi F, Yousefnia H, Mohammadianpanah M, Zolghadri S, Bahrami-Samani A, Ghannadi-Maragheh M. 177Lu/153Sm-Ethylenediamine tetramethylene phosphonic acid cocktail: A novel palliative treatment for patients with bone metastases. Cancer Biother Radiopharm. 2019 Jun;34(5):280-287.
  30. Pourhabib Z, Ranjbar H, Bahrami Samani A, Shokri A. Optimization of natural rhenium irradiation time to produce compositional radiopharmaceutical. Iran J Med Phys. 2018:16(5):362-367.
  31. Pourhabib Z, Ranjbar H, Bahrami Samani A, Shokri A. Experimental and theoretical study of rhenium radioisotopes production for manufacturing of new compositional radiopharmaceuticals. Appl Radiat Isot. 2019 Mar;145:176-179.
  32. Arano Y, Ono M, Wakisaka K, Uezono T, Akisawa H, Motonari Y, Makata Y, Konishi J, Yokoyama A. Synthesis and biodistribution studies of 186 Re complex of 1-hydroxyethylidene-1, 1-diphosphonate for treatment of painful osseous metastases. Radioisotopes (Tokyo). 1995;44(8):514-522.
  33. Das T, Banerjee S, Samuel G, Kothari K, Unni P, Sarma HD, Ramamoorthy N, Pillai MR. [186/188Re] rhenium-ethylene dicysteine (Re-Ec): preparation and evaluation for possible use in endovascular brachytherapy. Nucl Med Biol. 2000 Feb;27(2):189-97.
  34. Verdera E, Gaudiano J, Leon A, Martinez G, Robles A, Savio E, Leon E, McPherson DW, (Russ) Knapp Jr FF. Rhenium-188-HEDP-kit formulation and quality control. Radiochimica Acta. 1997;79(2):113-118.
  35. Zhi Y, Zho H, Nan L, Yun-Xia M, Yan Z. Preparation of 188Re-HEDP lyophilized kit for instant bone metastases therapy. Nucl Sci Tech. 2014;25(6):60302.

Files

Share

How to cite

Statistics