Seminars in Nuclear Medicine
Volume 40, Issue 2 , Pages 89-104 , March 2010

Systemic Metabolic Radiopharmaceutical Therapy in the Treatment of Metastatic Bone Pain

  • Fabio M. Paes, MD
  • ,
  • Aldo N. Serafini, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Aldo N. Serafini, MD, Division of Nuclear Medicine (D-57), Department of Radiology, University of Miami/Jackson Memorial Medical Center, 1611 NW 12th Avenue, Miami, FL 33136

References 

  1. Clines GA, Guise TA. Molecular mechanisms and treatment of bone metastasis. Expert Rev Mol Med. 2008;10:e7
  2. Clezardin P, Teti A. Bone metastasis: Pathogenesis and therapeutic implications. Clin Exp Metastasis. 2007;24:599–608
  3. Saarto T, Janes R, Tenhunen M, et al. Palliative radiotherapy in the treatment of skeletal metastases. Eur J Pain. 2002;6:323–330
  4. Lam MG, de Klerk JM, van Rijk PP, et al. Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases. Anticancer Agents Med Chem. 2007;7:381–397
  5. Hillegonds DJ, Franklin S, Shelton DK, et al. The management of painful bone metastases with an emphasis on radionuclide therapy. J Natl Med Assoc. 2007;99:785–794
  6. Serafini AN. Therapy of metastatic bone pain. J Nucl Med. 2001;42:895–906
  7. Christo PJ, Mazloomdoost D. Cancer pain and analgesia. Ann N Y Acad Sci. 2008;1138:278–298
  8. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management (Stepping up the quality of its evaluation). JAMA. 1995;274:1870–1873
  9. Thomas JR, Cooney GA, Slatkin NE. Palliative care and pain: New strategies for managing opioid bowel dysfunction. J Palliat Med. 2008;11(suppl 1):S1–S19quiz S21-S22
  10. Eisenberg E, McNicol E, Carr DB. Opioids for neuropathic pain. Cochrane Database Syst Rev. 2006;3:CD006146
  11. Mitra S. Opioid-induced hyperalgesia: Pathophysiology and clinical implications. J Opioid Manag. 2008;4:123–130
  12. Sacerdote P. Opioid-induced immunosuppression. Curr Opin Support Palliat Care. 2008;2:14–18
  13. Lin A, Ray ME. Targeted and systemic radiotherapy in the treatment of bone metastasis. Cancer Metastasis Rev. 2006;25:669–675
  14. Tong D, Gillick L, Hendrickson FR. The palliation of symptomatic osseous metastases: Final results of the study by the Radiation Therapy Oncology Group. Cancer. 1982;50:893–899
  15. Poulter CA, Cosmatos D, Rubin P, et al. A report of RTOG 8206: A phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases. Int J Radiat Oncol Biol Phys. 1992;23:207–214
  16. Dy SM, Asch SM, Naeim A, et al. Evidence-based standards for cancer pain management. J Clin Oncol. 2008;26:3879–3885
  17. Jeremic B. Single fraction external beam radiation therapy in the treatment of localized metastatic bone pain (A review). J Pain Symptom Manage. 2001;22:1048–1058
  18. Auclerc G, Antoine EC, Cajfinger F, et al. Management of advanced prostate cancer. Oncologist. 2000;5:36–44
  19. Kudachadkar R, O'Regan RM. Aromatase inhibitors as adjuvant therapy for postmenopausal patients with early stage breast cancer. CA Cancer J Clin. 2005;55:145–163
  20. Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer. 2001;91:1191–1200
  21. Berenson JR. Zoledronic acid in cancer patients with bone metastases: Results of phase I and II trials. Semin Oncol. 2001;28(suppl 6):25–34
  22. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: A pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001;19:558–567
  23. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: A randomized, double-blind, multicenter, comparative trial. Cancer. 2003;98:1735–1744
  24. Furlow B. Zoledronic acid palliation in bone-metastatic breast cancer. Lancet Oncol. 2006;7:894
  25. Fulfaro F, Leto G, Badalamenti G, et al. The use of zoledronic acid in patients with bone metastases from prostate carcinoma: Effect on analgesic response and bone metabolism biomarkers. J Chemother. 2005;17:555–559
  26. Berenson JR, Rajdev L, Broder M. Treatment strategies for skeletal complications of cancer. Cancer Biol Ther. 2006;5:1074–1077
  27. Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: A systematic review. Lancet Oncol. 2005;6:392–400
  28. Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 2004;45:1358–1365
  29. Lewington VJ. Cancer therapy using bone-seeking isotopes. Phys Med Biol. 1996;41:2027–2042
  30. Lambert B, de Klerk JM. Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. Nucl Med Commun. 2006;27:223–229
  31. Ferro-Flores G, Arteaga de Murphy C. Pharmacokinetics and dosimetry of 188Re-pharmaceuticals. Adv Drug Deliv Rev. 2008;60:1389–1401
  32. Kavakli K, Aydogdu S, Taner M, et al. Radioisotope synovectomy with rhenium 186 in haemophilic synovitis for elbows, ankles and shoulders. Haemophilia. 2008;14:518–523
  33. Bucerius J, Wallny T, Brackmann HH, et al. Rhenium-186 hydroxyethylidenediphosphonate (186Re HEDP) for the treatment of hemophilic arthropathy: First results. Clin J Pain. 2007;23:612–618
  34. Dobert N, Martin H, Kranert WT, et al. Re-186 HEDP conditioning therapy in patients with advanced acute lymphoblastic leukemia before allogeneic bone marrow transplantation. Clin Nucl Med. 2003;28:738–742
  35. Rodriguez V, Anderson PM, Litzow MR, et al. Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and hematopoietic stem cell infusion for acute myelogenous leukemia. Leuk Lymphoma. 2006;47:1583–1592
  36. Rodriguez V, Erlandson L, Arndt CA, et al. Low toxicity and efficacy of (153)samarium-EDTMP and melphalan as a conditioning regimen for secondary acute myelogenous leukemia. Pediatr Transplant. 2005;9:122–126
  37. Luo TY, Tang IC, Wu YL, et al. Evaluating the potential of 188Re-SOCTA-trastuzumab as a new radioimmunoagent for breast cancer treatment. Nucl Med Biol. 2009;36:81–88
  38. Casaco A, Lopez G, Garcia I, et al. Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188 Re in adult recurrent high-grade glioma. Cancer Biol Ther. 2008;7:333–339
  39. Torres-Garcia E, Ferro-Flores G, Arteaga de Murphy C, et al. Biokinetics and dosimetry of 188Re-anti-CD20 in patients with non-Hodgkin's lymphoma: Preliminary experience. Arch Med Res. 2008;39:100–109
  40. Fani M, Xanthopoulos S, Archimandritis SC, et al. Biodistribution and scintigraphic studies of 153Sm-labeled anti-CEA monoclonal antibody for radioimmunoscintigraphy and radioimmunotherapy. Anticancer Res. 2003;23:2195–2199
  41. Bodei L, Lam M, Chiesa C, et al. EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging. 2008;35:1934–1940
  42. Silberstein EB, Taylor AT. EANM procedure guidelines for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging. 2003;30:BP7–B11
  43. Kraeber-Bodere F, Campion L, Rousseau C, et al. Treatment of bone metastases of prostate cancer with strontium-89 chloride: Efficacy in relation to the degree of bone involvement. Eur J Nucl Med. 2000;27:1487–1493
  44. Gkialas I, Iordanidou L, Galanakis I, et al. The use of radioisotopes for palliation of metastatic bone pain. J BUON. 2008;13:177–183
  45. Farhanghi M, Holmes RA, Volkert WA, et al. Samarium-153-EDTMP: Pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. J Nucl Med. 1992;33:1451–1458
  46. De Klerk JM, Zonnenberg BA, Blijham GH, et al. Treatment of metastatic bone pain using the bone seeking radiopharmaceutical Re-186-HEDP. Anticancer Res. 1997;17:1773–1777
  47. Collins C, Eary JF, Donaldson G, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: A phase I/II trial. J Nucl Med. 1993;34:1839–1844
  48. Taylor AJ. Strontium-89 for the palliation of bone pain due to metastatic disease. J Nucl Med. 1994;35:2054
  49. Blake GM, Zivanovic MA, Blaquiere RM, et al. Strontium-89 therapy: Measurement of absorbed dose to skeletal metastases. J Nucl Med. 1988;29:549–557
  50. Fuster D, Herranz D, Vidal-Sicart S, et al. Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients. Nucl Med Commun. 2000;21:623–626
  51. Turner SL, Gruenewald S, Spry N, et al. Less pain does equal better quality of life following strontium-89 therapy for metastatic prostate cancer. Br J Cancer. 2001;84:297–302
  52. Dafermou A, Colamussi P, Giganti M, et al. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med. 2001;28:788–798
  53. Ashayeri E, Omogbehin A, Sridhar R, et al. Strontium 89 in the treatment of pain due to diffuse osseous metastases: A university hospital experience. J Natl Med Assoc. 2002;94:706–711
  54. Zorga P, Birkenfeld B. Strontium-89 in palliative treatment of painful bone metastases. Ortop Traumatol Rehabil. 2003;5:369–373
  55. Baczyk M, Milecki P, Baczyk E, et al. The effectiveness of strontium 89 in palliative therapy of painful prostate cancer bone metastases. Ortop Traumatol Rehabil. 2003;5:364–368
  56. Gunawardana DH, Lichtenstein M, Better N, et al. Results of strontium-89 therapy in patients with prostate cancer resistant to chemotherapy. Clin Nucl Med. 2004;29:81–85
  57. Liepe K, Kotzerke J. A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases. Nucl Med Commun. 2007;28:623–630
  58. Ma YB, Yan WL, Dai JC, et al. Strontium-89: A desirable therapeutic for bone metastases of prostate cancer. Zhonghua Nan Ke Xue. 2008;14:819–822
  59. Serafini AN, Houston SJ, Resche I, 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;16:1574–1581
  60. Tian JH, Zhang JM, Hou QT, 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
  61. Dolezal J. Systemic radionuclide therapy with samarium-153-EDTMP for painful bone metastases. Nucl Med Rev Cent East Eur. 2000;3:161–163
  62. Wang RF, Zhang CL, Zhu SL, et al. A comparative study of samarium-153-ethylenediaminetetramethylene phosphonic acid with pamidronate disodium in the treatment of patients with painful metastatic bone cancer. Med Princ Pract. 2003;12:97–101
  63. Sapienza MT, Ono CR, Guimaraes MI, et al. Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy. Rev Hosp Clin Fac Med Sao Paulo. 2004;59:321–328
  64. Etchebehere EC, Pereira Neto CA, Lima MC, et al. Treatment of bone pain secondary to metastases using samarium-153-EDTMP. Sao Paulo Med J. 2004;122:208–212
  65. Sartor O, Reid RH, Hoskin PJ, et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004;63:940–945
  66. Tripathi M, Singhal T, Chandrasekhar N, et al. Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases. Indian J Cancer. 2006;43:86–92
  67. Dolezal J, Vizda J, Odrazka K. Prospective evaluation of samarium-153-EDTMP radionuclide treatment for bone metastases in patients with hormone-refractory prostate cancer. Urol Int. 2007;78:50–57
  68. Kolesnikov-Gauthier H, Carpentier P, Depreux P, et al. Evaluation of toxicity and efficacy of 186Re-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer. J Nucl Med. 2000;41:1689–1694
  69. Tennvall J, Abrahamsson PA, Ahlgren G, et al. Palliative radiation with a radiolabeled diphosphonate (rhenium-186 etidronate) in patients with hormone-refractory disseminated prostate carcinoma. Scand J Urol Nephrol. 2000;34:188–193
  70. Kucuk NO, Ibis E, Aras G, et al. Palliative analgesic effect of Re-186 HEDP in various cancer patients with bone metastases. Ann Nucl Med. 2000;14:239–245
  71. Sciuto R, Tofani A, Festa A, et al. Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases. J Nucl Med. 2000;41:647–654
  72. Sciuto R, Festa A, Pasqualoni R, et al. Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients. Breast Cancer Res Treat. 2001;66:101–109
  73. Han SH, de Klerk JM, Tan S, 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;43:1150–1156
  74. Leondi AH, Souvatzoglou MA, Rapti AS, et al. Palliative treatment of painful disseminated bone metastases with 186Rhenium-HEDP in patients with lung cancer. Q J Nucl Med Mol Imaging. 2004;48:211–219
  75. Pons F, Herranz R, Garcia A, et al. Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer. Eur J Nucl Med. 1997;24:1210–1214
  76. Baziotis N, Yakoumakis E, Zissimopoulos A, et al. Strontium-89 chloride in the treatment of bone metastases from breast cancer. Oncology. 1998;55:377–381
  77. Laing AH, Ackery DM, Bayly RJ, et al. Strontium-89 chloride for pain palliation in prostatic skeletal malignancy. Br J Radiol. 1991;64:816–822
  78. Lee CK, Aeppli DM, Unger J, et al. Strontium-89 chloride (Metastron) for palliative treatment of bony metastases (The University of Minnesota experience). Am J Clin Oncol. 1996;19:102–107
  79. Silberstein EB, Williams C. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med. 1985;26:345–348
  80. Mertens WC, Stitt L, Porter AT. Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: A dose response relationship?. Am J Clin Oncol. 1993;16:238–242
  81. Nilsson S, Strang P, Ginman C, et al. Palliation of bone pain in prostate cancer using chemotherapy and strontium-89 (A randomized phase II study). J Pain Symptom Manage. 2005;29:352–357
  82. Windsor PM. Predictors of response to strontium-89 (Metastron) in skeletal metastases from prostate cancer: Report of a single centre's 10-year experience. Clin Oncol (R Coll Radiol). 2001;13:219–227
  83. Eary JF, Collins C, Stabin M, et al. Samarium-153-EDTMP biodistribution and dosimetry estimation. J Nucl Med. 1993;34:1031–1036
  84. Alberts AS, Smit BJ, Louw WK, et al. Dose response relationship and multiple dose efficacy and toxicity of samarium-153-EDTMP in metastatic cancer to bone. Radiother Oncol. 1997;43:175–179
  85. Serafini AN. Samarium Sm-153 lexidronam for the palliation of bone pain associated with metastases. Cancer. 2000;88(suppl 12):2934–2939
  86. Resche I, Chatal JF, Pecking A, et al. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997;33:1583–1591
  87. Menda Y, Bushnell DL, Williams RD, et al. Efficacy and safety of repeated samarium-153 lexidronam treatment in a patient with prostate cancer and metastatic bone pain. Clin Nucl Med. 2000;25:698–700
  88. 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;109:637–643
  89. Maxon HR, Deutsch EA, Thomas SR, et al. Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: Human biodistribution and dosimetric studies. Radiology. 1988;166:501–507
  90. de Klerk JM, Zonnenberg BA, van het Schip AD, et al. Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. Eur J Nucl Med. 1994;21:1114–1120
  91. de Klerk JM, van het Schip AD, Zonnenberg BA, et al. Phase 1 study of rhenium-186-HEDP in patients with bone metastases originating from breast cancer. J Nucl Med. 1996;37:244–249
  92. Maxon HR, Schroder LE, Hertzberg VS, 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;32:1877–1881
  93. Maxon HR, Thomas SR, Hertzberg VS, et al. Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases. Semin Nucl Med. 1992;22:33–40
  94. Englaro EE, Schroder LE, Thomas SR, et al. Safety and efficacy of repeated sequential administrations of Re-186(Sn)HEDP as palliative therapy for painful skeletal metastases (Initial case reports of two patients). Clin Nucl Med. 1992;17:41–44
  95. Sundram F, Chau TC, Onkhuudai P, et al. Preliminary results of transarterial rhenium-188 HDD lipiodol in the treatment of inoperable primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2004;31:250–257
  96. Bernal P, Raoul JL, Vidmar G, et al. Intra-arterial rhenium-188 lipiodol in the treatment of inoperable hepatocellular carcinoma: Results of an IAEA-sponsored multination study. Int J Radiat Oncol Biol Phys. 2007;69:1448–1455
  97. De Decker M, Bacher K, Thierens H, et al. In vitro and in vivo evaluation of direct rhenium-188-labeled anti-CD52 monoclonal antibody alemtuzumab for radioimmunotherapy of B-cell chronic lymphocytic leukemia. Nucl Med Biol. 2008;35:599–604
  98. Palmedo H, Guhlke S, Bender H, et al. Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med. 2000;27:123–130
  99. Liepe K, Kropp J, Runge R, et al. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer. 2003;89:625–629
  100. Palmedo H, Manka-Waluch A, Albers P, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: Tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol. 2003;21:2869–2875
  101. Li S, Liu J, Zhang H, et al. Rhenium-188 HEDP to treat painful bone metastases. Clin Nucl Med. 2001;26:919–922
  102. Baczyk M, Czepczynski R, Milecki P, et al. 89Sr versus 153Sm-EDTMP: Comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma. Nucl Med Commun. 2007;28:245–250
  103. Sciuto R, Festa A, Tofani A, et al. Platinum compounds as radiosensitizers in strontium-89 metabolic radiotherapy. Clin Ter. 1998;149:43–47
  104. Tu SM, Millikan RE, Mengistu B, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: A randomised phase II trial. Lancet. 2001;357:336–341
  105. Akerley W, Butera J, Wehbe T, et al. A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer. 2002;94:1654–1660
  106. Pagliaro LC, Delpassand ES, Williams D, et al. A Phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases. Cancer. 2003;97:2988–2994
  107. Amato RJ, Hernandez-McClain J, Henary H. Bone-targeted therapy: Phase II study of strontium-89 in combination with alternating weekly chemohormonal therapies for patients with advanced androgen-independent prostate cancer. Am J Clin Oncol. 2008;31:532–538
  108. Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med. 2005;46(suppl 1):38S–47S
  109. Storto G, Klain M, Paone G, et al. Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases. Bone. 2006;39:35–41
  110. Lam MG, Dahmane A, Stevens WH, et al. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases. Eur J Nucl Med Mol Imaging. 2008;35:756–765
  111. Marcus CS, Saeed S, Mlikotic A, et al. Lack of effect of a bisphosphonate (pamidronate disodium) infusion on subsequent skeletal uptake of Sm-153 EDTMP. Clin Nucl Med. 2002;27:427–430

PII: S0001-2998(09)00101-9

doi: 10.1053/j.semnuclmed.2009.10.003

Seminars in Nuclear Medicine
Volume 40, Issue 2 , Pages 89-104 , March 2010