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Treatment of Bone Metastasis with Bone-Targeting Radiopharmaceuticals

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Abstract

Bone is a common metastatic site of cancer. Bone metastasis reduces life expectancy and results in serious symptoms and complications such as bone pain, pathological fractures, and spinal cord compression, decreasing quality of life by restricting sleep and mobility. Treatment for bone metastasis includes drugs (pure analgesics, hormones, cytotoxic chemotherapy, and bisphosphonates, among others), external radiation therapy, surgery, and radionuclide therapy using bone-targeting radiopharmaceuticals. Particulate radiation with α- or β-rays is used as a bone-targeting radiopharmaceutical in radionuclide therapy. β-Emitters have lower energy and a longer range than α-emitters and have less tumoricidal activity and deliver more radiation to adjacent normal tissue. Therefore, the main therapeutic effect of bone-targeting β-emitters such as 89Sr-dichloride is bone pain palliation rather than enhanced survival. In contrast, α-emitters such as 223Ra-dichloride have high energy and a short range, resulting in greater tumoricidal activity and less radiation damage to adjacent normal tissue. Treatment with bone-targeting α-emitters can improve survival and decrease bone pain. This review focuses on the principles and clinical utility of several clinically available bone-targeting radiopharmaceuticals in metastatic bone disease.

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References

  1. Randall RL. Metastatic bone disease—an integrated approach to patient care: Springer; 2016.

  2. Jehn CF, Diel IJ, Overkamp F, Kurth A, Schaefer R, Miller K, et al. Management of metastatic bone disease algorithms for diagnostics and treatment. Anticancer Res. 2016;36:2631–7.

    PubMed  CAS  Google Scholar 

  3. Buckwalter JA, Brandser EA. Metastatic disease of the skeleton. Am Fam Physician. 1997;55:1761.

    PubMed  CAS  Google Scholar 

  4. Buga S, Sarria JE. The management of pain in metastatic bone disease. Cancer Control. 2012;19:154–66.

    Article  PubMed  CAS  Google Scholar 

  5. Chiacchio S, Mazzarri S, Lorenzoni A, Nyakale N, Boni G, Borsò E, et al. Radionuclide therapy and integrated protocols for bone metastases. Q J Nucl Med Mol Imaging. 2011;55:431–47.

    PubMed  CAS  Google Scholar 

  6. Silberstein EB. Teletherapy and radiopharmaceutical therapy of painful bone metastases. Semin Nucl Med. 2005;35:152–8.

    Article  PubMed  Google Scholar 

  7. Srivastava SC. The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter tin-117m. Braz Arch Biol Technol. 2007;50:49–62.

    Article  Google Scholar 

  8. Pandit-Taskar N, Larson SM, Carrasquillo JA. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, part 1: α therapy with 223Ra-chloride. J Nucl Med. 2014;55:268–74.

    Article  PubMed  CAS  Google Scholar 

  9. Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 2004;45:1358–65.

    PubMed  CAS  Google Scholar 

  10. Zhu XC, Zhang JL, Ge CT, Yu YY, Wang P, Yuan TF, et al. Advances in cancer pain from bone metastasis. Drug Des Devel Ther. 2015;18(9):4239–45.

    Google Scholar 

  11. Urch C. The pathophysiology of cancer-induced bone pain: current understanding. Palliat Med. 2004;18:267–74.

    Article  PubMed  Google Scholar 

  12. Honore P, Rogers SD, Schwei MJ, Salak-Johnson JL, Luger NM, Sabino MC, et al. Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience. 2000;98:585–98.

    Article  PubMed  CAS  Google Scholar 

  13. Bodei L, Lam M, Chiesa C, Flux G, Brans B, Chiti A, et al. EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging. 2008;35:1934–40.

    Article  PubMed  Google Scholar 

  14. Fuster D, Herranz R, Alcover J, Mateos JJ, Martín F, Vidal-Sicart S, et al. Treatment of metastatic bone pain with repeated doses of strontium-89 in patients with prostate neoplasm. Rev Esp Med Nucl. 2000;19:270–4.

    Article  PubMed  CAS  Google Scholar 

  15. Sartor O, Reid RH, Bushnell DL, et al. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer. 2007;109:637–43.

    Article  PubMed  CAS  Google Scholar 

  16. Friedell HL, Storaasli JP. The use of radioactive phosphorus in the treatment of carcinoma of the breast with widespread metastases to bone. AJR. 1950;64:559–75.

    CAS  Google Scholar 

  17. Maxfield JR, Maxfield JG, Maxfield WS. The use of radioactive phosphorus and testosterone in metastatic bone lesions from breast and prostate. South Med J. 1958;51:320–7.

    Article  PubMed  Google Scholar 

  18. Miller AD. Radiophosphorus (P32) treatment in carcinoma of the breast and prostate: report of 39 cases. J Am Osteopath Assoc. 1974;74:217–22.

    PubMed  CAS  Google Scholar 

  19. Cheung A, Driedger AA. Evaluation of radioactive phosphorus in the palliation of metastatic bone lesions from carcinoma of the breast and prostate. Radiology. 1980;134:209–12.

    Article  PubMed  CAS  Google Scholar 

  20. Silberstein EB. The treatment of painful osseous metastases with phosphorus-32-labeled phosphates. Semin Oncol. 1993;20(supple 2):10–21.

    PubMed  CAS  Google Scholar 

  21. Nair N. Relative efficacy of 32P and 89Sr in palliation in skeletal metastases. J Nucl Med. 1999;40:256–61.

    PubMed  CAS  Google Scholar 

  22. Fettich J, Padhy A, Nair N, Morales R, Tanumihardja M, Riccabonna G, et al. Comparative clinical efficacy and safety of phosphorus-32 and strontium-89 in the palliative treatment of metastatic bone pain: results of an IAEA coordinated research project. World J Nucl Med. 2003;2:226–31.

    Google Scholar 

  23. Blake GM, Zivanovic MA, McEwan AJ, Ackery DM. Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. Eur J Nucl Med. 1986;12:447–54.

    PubMed  CAS  Google Scholar 

  24. Sciuto R, Festa A, Pasqualoni R, Semprebene A, Rea S, Bergomi S, et al. Metastatic bone pain palliation with 89-Sr and 186-re-HEDP in breast cancer patients. Br Cancer Res Treat. 2001;66:101–9.

    Article  CAS  Google Scholar 

  25. Zenda S, Nakagami Y, Toshima M, Arahira S, Kawashima M, Matsumoto Y. At al. Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with multiple bone metastases. Int J Clin Oncol. 2014;19:739–43.

    Article  PubMed  CAS  Google Scholar 

  26. Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol. 2005;6:392–400.

    Article  PubMed  CAS  Google Scholar 

  27. Mertens WC, Stitt L, Porter AT. Strontium-89 therapy and relief of pain in patients with prostate carcinoma metastatic to bone: a dose response relationship? Am J Clin Oncol. 1993;16:238–42.

    Article  PubMed  CAS  Google Scholar 

  28. Silberstein EB, Williams C. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med. 1985;26:345–8.

    PubMed  CAS  Google Scholar 

  29. Robinson RG, Preston DF, Spicer JA, Baxter KG. Radionuclide therapy of intractable bone pain: emphasis on strontium-89. Semin Nucl Med. 1992;22:28–32.

    Article  PubMed  CAS  Google Scholar 

  30. McEwan AJB, Porter AT, Vennes DM, Amyotte G. An evaluation of the safety and efficacy of treatment with strontium-89 in patients who have previously received wide field radiotherapy. Antibody Immunoconjugates Radiopharm. 1990;3:91–8.

    Google Scholar 

  31. Zyskowski A, Lamb D, Morum P, Hamilton D, Johnson C. Strontium-89 treatment for prostate cancer bone metastases: does a prostate-specific antigen response predict for improved survival? Australas Radiol. 2001;45:39–42.

    Article  PubMed  CAS  Google Scholar 

  32. Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, et al. Bone-targeted therapy for androgen-independent carcinoma of the prostate: a randomized phase II trial. Lancet. 2001;357:336–41.

    Article  PubMed  CAS  Google Scholar 

  33. Buchali K, Correns HJ, Schuerer M, Schnorr D, Lips H, Sydow K. Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med. 1988;14:349–51.

    PubMed  CAS  Google Scholar 

  34. Dickie GJ, Macfarlane D. Strontium and samarium therapy for bone metastases from prostate carcinoma. Australas Radiol. 1999;43:476–9.

    Article  PubMed  CAS  Google Scholar 

  35. Liepe K, Franke WG, Kropp J, Koch R, Runge R, Hliscs R. Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases. Nuklearmedizin. 2000;39:146–51.

    Article  PubMed  CAS  Google Scholar 

  36. Maxon HR III, Schroder LE, Thomas SR, et al. Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology. 1990;176:155–9.

    Article  PubMed  Google Scholar 

  37. Giannakenas C, Kalofonos HP, Apostolopoulos DJ, Zarakovitis J, Kosmas C, Vassilakos PJ. Preliminary results of the use of re-186-HEDP for palliation of pain in patients with metastatic bone disease. Am J Clin Oncol. 2000;23:83–8.

    Article  PubMed  CAS  Google Scholar 

  38. Kolesnikov-Gauthier H, Carpentier P, Depreux P, Vennin P, Caty A, Sulman C. Evaluation of toxicity and efficacy of 186Re-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer. J Nucl Med. 2000;41:1689–94.

    PubMed  CAS  Google Scholar 

  39. Sciuto R, Tofani A, Festa A, Giannarelli D, Pasqualoni R, Maini CL. Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases. J Nucl Med. 2000;41:647–54.

    PubMed  CAS  Google Scholar 

  40. Quirijnen JM, Han SH, Zonnenberg BA, de Klerk JM, van het Schip AD, van Dijk A, et al. Efficacy of rhenium-186-etidronate in prostate cancer patients with metastatic bone pain. J Nucl Med. 1996;37:1511–5.

    PubMed  CAS  Google Scholar 

  41. Han SH, Zonneberg BA, de Klerk JM, Quirijnen JM, van het Schip AD, van Dijk A, et al. 186Re-etidronate in breast cancer patients with metastatic bone pain. J Nucl Med. 1999;40:639–42.

    PubMed  CAS  Google Scholar 

  42. Maxon HR III, Schroder LE, Hertzberg VS, Thomas SR, Englaro EE, Samaratunga R, et al. Rhenium-186(Sn) HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J Nucl Med. 1991;32:1877–81.

    PubMed  Google Scholar 

  43. Han SH, de Klerk JM, Tan S, van het Schip AD, Derksen BH, van Dijk A, et al. The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo controlled rhenium study. J Nucl Med. 2002;43:1150–6.

    PubMed  CAS  Google Scholar 

  44. Den RB, Doyle LA, Knudsen E. Practical guide to the use of radium-223 dichloride. Can J Urol. 2014;21(Suppl 1):70–6.

    PubMed  Google Scholar 

  45. Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, et al. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997;33:1583–91.

    Article  PubMed  CAS  Google Scholar 

  46. Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol. 1998;16:1574–81.

    Article  PubMed  CAS  Google Scholar 

  47. Tian JH, Zhang JM, Hou QT, Oyang QH, Wang JM, Luan ZS, et al. Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China. Eur J Nucl Med. 1999;26:2–7.

    Article  PubMed  CAS  Google Scholar 

  48. Janeway HH. Radium therapy in cancer at the memorial hospital, New York; first report, 1915–1916. New York: Paul B. Hoeber; 1917.

    Google Scholar 

  49. Henriksen G, Breistøl K, Bruland ØS, Fodstad Ø, Larsen RH. Significant antitumor effect from bone-seeking, alpha-particle-emitting (223)Ra demonstrated in an experimental skeletal metastases model. Cancer Res. 2002;62:3120–5.

    PubMed  CAS  Google Scholar 

  50. Nilsson S, Larsen RH, Fosså SD, Balteskard L, Borch KW, Westlin JE. At al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11:4451–9.

    Article  PubMed  CAS  Google Scholar 

  51. Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, et al. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007;8:587–94.

    Article  PubMed  CAS  Google Scholar 

  52. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  PubMed  CAS  Google Scholar 

  53. Carrasquillo JA, O’Donoghue JA, Pandit-Taskar N, Humm JL, Rathkopf DE, Slovin SF, et al. Phase I pharmacokinetic and biodistribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1384–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Lassmann M, Nosske D. Dosimetry of 223Ra-chloride: dose to normal organs and tissues. Eur J Nucl Med Mol Imaging. 2013;40:207–12.

    Article  PubMed  CAS  Google Scholar 

  55. Bruland ØS, Nilsson S, Fisher DR, Larsen RH. High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res. 2006;12(20 Pt 2):6250s–7s.

    Article  PubMed  CAS  Google Scholar 

  56. Dauer LT, Williamson MJ, Humm J, O’Donoghue J, Ghani R, Awadallah R, et al. Radiation safety considerations for the use of 223RaCl2 DE in men with castration-resistant prostate cancer. Health Phys. 2014;106:494–504.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Bayer HealthCare. Xofigo (radium Ra 223 dichloride) Injection, for intravenous use: highlights of prescribing information. 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203971lbl.pdf. Accessed 15 Nov 2017.

  58. Readler LA. Xofigo (radium Ra 223 dichloride): the first alpha particle-emitting radioactive agent for the treatment of castrationresistant prostate cancer with symptomatic bone metastases. American Health and Drugs Benefits. Available at: http://www.ahdbonline.com/articles/1431-article-1431. Accessed 15 Nov 2017.

  59. Parker C, Zhan L, Cislo P, Reuning-Scherer J, Vogelzang NJ, Nilsson S, et al. Effect of radium-223 dichloride (Ra-223) on hospitalisation: an analysis from the phase 3 randomised Alpharadin in symptomatic prostate cancer patients (ALSYMPCA) trial. Eur J Cancer. 2017;71:1–6.

    Article  PubMed  CAS  Google Scholar 

  60. Coleman R, Aksnes AK, Naume B, Garcia C, Jerusalem G, Piccart M, et al. A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease. Breast Cancer Res Treat. 2014;145:411–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Choi, J.Y. Treatment of Bone Metastasis with Bone-Targeting Radiopharmaceuticals. Nucl Med Mol Imaging 52, 200–207 (2018). https://doi.org/10.1007/s13139-017-0509-2

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