Skip to main content
SpringerLink
Log in

Targeted Radionuclide Therapy for Bone Metastasis

  • Reference work entry
  • First Online:
Nuclear Oncology

  • 2015 Accesses

Abstract

Bone metastases markedly reduce the quality of life due to bone pain, pathologic fractures, loss of mobility, and hypercalcemia. A graded three-step approach, as recommended by the World Health Organization (WHO), is used to treat pain according to its severity. Nonsteroidal anti-inflammatory drugs are used in patients with mild to moderate pain. When pain persists or increases, a weak opioid such as codeine or hydrocodone is added. Higher doses or more potent opioids are used if the pain persists or becomes more severe. Bisphosphonates (BPs) are useful in the treatment of osteoporosis and metastatic disease by decreasing the resorption of the bone. BPs bind to bone mineral and directly interfere with the activation of osteoclasts. They are internalized by osteoclasts and inhibit specific biochemical and metabolic pathways in these cells; they also reduce skeletal complications and reduce the rate of development of new lesions and delay progression in bone metastases. External beam radiation therapy given as a single or multifractionated dose is an effective treatment and provides early relief, especially for localized bone pain due to bone metastasis. Therapy with bone-seeking radiopharmaceuticals is effective for reducing pain in patients with widespread, painful bone metastases from various malignancies particularly prostate cancer. A variety of radiopharmaceuticals have been used and tested, including many beta-emitting nuclides and alpha emitting radium-223 (223Ra) dichloride. Each of these agents target the bone by chemical bonding or adsorbing to the trabecular surface of the bone, the metal-chelated radiotracer to the trabecular surface, while 32P-sodium orthophosphate and 89Sr-chloride distribute more widely throughout the bone. 89Sr-chloride and 153Sm-EDTMP are two FDA-approved beta-emitting radiopharmaceuticals that have largely replaced 32P-sodium orthophosphate in the treatment of metastatic bone pain in the United States. More recently, alpha-emitting 223Ra-dichloride has been used in symptomatic castration-resistant prostate cancer (CRPC). The onset of pain relief commonly occurs within 7–21 days. Re-treatment is possible after allowing for marrow recovery; however, multiple therapies require consideration of cumulative marrow toxicity.

89Sr-chloride and 153Sm-EDTMP have been used extensively, primarily for the treatment of bone pain from breast and prostate cancer due to the presence of osteoblastic disease that enables high uptake of the agents. Radionuclide therapy may be used alone or in combination with chemotherapy or radiation therapy to enhance pain relief and delay onset of new pain; consideration needs to be directed to overlapping or cumulative toxicities especially in the marrow that may require supportive treatment. Patients most suitable for bone pain therapy are those with multiple sites of bone metastases confirmed by a bone scan showing focal sites of increased radiopharmaceutical uptake and those who have symptoms related to osseous disease that requires increased doses of pain medication or is refractory to pain medication. 223Ra is an alpha-emitting radionuclide that accumulates in the bone as it is analogous to calcium. The high linear energy transfer of alpha radiation leads to double-strand DNA breaks within the cells. While effective for pain palliation, it has also shown survival benefit in those with metastatic osseous disease from prostate cancer. However, it is currently approved for use only in symptomatic CRPC patients who have no other visceral diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 949.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

153Sm-EDTMP:

153Sm- Ethylenediamine Tetramethylene Phosphoric Acid

117mSn-DTPA:

117mSn-Diethylenetriaminepentaacetic acid

[18F]FDG:

2-deoxy-2-[18F]fluoro-D-glucose

186Re-HEDP:

186Re Hydroxyethylidene diphosphonate

AEs:

Adverse events

ALARA:

As low as reasonably achievable

ALP:

Alkaline phosphatase

ALSYMPCA:

Alpharadin in Symptomatic Prostate Cancer Patients

ATP:

Adenosine triphosphate

BPs:

Bisphosphonates

CD:

Cluster of differentiation

CPFS:

Clinical progression-free survival

CRPC:

Castration-resistant prostate cancer

DLT:

Dose-limiting toxicity

DNA:

Deoxyribonucleic acid

DOTMP:

1,4,7,10 - tetraazacyclododecane -1,4,7,10-tetramethylene phosphonic acid

DTPMP:

Diethylenetriamine pentakis (methylphosphonic acid)

EBRT:

External beam radiation therapy

ECM:

Extracellular matrix

ER:

Estrogen receptor

FDA:

United States Food and Drug Administration

FPPS:

Farnesyl pyrophosphate synthase

GFAP:

Glial fibrillary acidic protein

GFR:

Glomerular filteration rate

GI:

Gastro-intestinal

GMP:

Good manufacturing practices

GTP:

Guanosine Triphosphate

Gy:

Gray unit (ionizing radiation dose in the International System of Units, corresponding to the absorption of one joule of radiation energy per kilogram of matter)

ICER:

Incremental cost-effectiveness ratio

IMRT:

Intensity modulated radiotherapy

IV:

Intravenous

LDH:

Lactate dehydrogenase

LET:

Linear energy transfer

99mTc-MDP:

99mTc-Methylene Diphosphonate

MTD:

Maximum tolerated dose

NCCN:

National Comprehensive Cancer Network

NRC:

Nuclear Regulatory Commission

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OPGL:

Osteoprotegerin ligand

OS:

Overall survival

PFS:

Progression-free survival

PGA:

Physician’s global assessment

PSA:

Prostate-specific antigen

PTHrP:

Parathyroid hormone-related protein

QALY:

Quality-adjusted life-year

QOL:

Quality of life

RANK:

Receptor activator of nuclear factor kappa-B

RANKL:

Receptor activator of nuclear factor kappa-B ligand

RP:

Radiopharmaceutical

RT:

Radiotherapy

SAE:

Serious adverse event

SBRT:

Stereotactic body radiation therapy

SEP:

Sum of effect product

SRE:

Skeletal relevant events

TGF-β:

Transforming growth factor-beta

TNF:

Tumor necrosis Factor

TTHMP:

Triethylenetetraminehexamethylene phosphonic acid

ULN:

Upper limit of normal

uNTX-1:

Urinary N-telopeptide of type 1

VAS-AUPC:

Visual analog scale-area under the pain curve

WBC:

White blood cell

WHO:

World Health Organization

XRT:

External radiation therapy

ZA:

Zoledronic acid

References

  1. Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–76.

    Article  CAS  PubMed  Google Scholar 

  2. Frassica FJ, Gitelis S, Sim FH. Metastatic bone disease: general principles, pathophysiology, evaluation, and biopsy. Instr Course Lect. 1992;41:293–300.

    CAS  PubMed  Google Scholar 

  3. Hage WD, Aboulafia AJ, Aboulafia DM. Incidence, location, and diagnostic evaluation of metastatic bone disease. Orthop Clin North Am. 2000;31(4):515–28.vii.

    Article  CAS  PubMed  Google Scholar 

  4. WHO. World health organization. Cancer pain relief. Geneva: World Health Organization; 1986. http://www.WHO.int/cancer/palliative/painladder/en/.

    Google Scholar 

  5. NCCN practice guidelines: adult cancer pain. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

  6. Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12(8):895–904.

    Article  CAS  PubMed  Google Scholar 

  7. Steeg PS. Targeting metastasis. Nat Rev Cancer. 2016;16(4):201–18.

    Article  CAS  PubMed  Google Scholar 

  8. Choong PF. The molecular basis of skeletal metastases. Clin Orthop Relat Res. 2003;415(Suppl):S19–31.

    Article  Google Scholar 

  9. Zhao Y, Wang Y, Liu J. P-selectin and tumor metastasis. Zhonghua Jie He He Hu Xi Za Zhi. 2001;24(9):568–70.

    CAS  PubMed  Google Scholar 

  10. Yeatman TJ, Nicolson GL. Molecular basis of tumor progression: mechanisms of organ-specific tumor metastasis. Semin Surg Oncol. 1993;9(3):256–63.

    CAS  PubMed  Google Scholar 

  11. Tang DG, Honn KV. Adhesion molecules and tumor metastasis: an update. Invasion Metastasis. 1994;14(1–6):109–22.

    CAS  PubMed  Google Scholar 

  12. Laubli H, Borsig L. Selectins promote tumor metastasis. Semin Cancer Biol. 2010;20(3):169–77.

    Article  PubMed  CAS  Google Scholar 

  13. Kim YJ, et al. P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci U S A. 1998;95(16):9325–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Coupland LA, Chong BH, Parish CR. Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. Cancer Res. 2012;72(18):4662–71.

    Article  CAS  PubMed  Google Scholar 

  15. Koukoulis GK, Patriarca C, Gould VE. Adhesion molecules and tumor metastasis. Hum Pathol. 1998;29(9):889–92.

    Article  CAS  PubMed  Google Scholar 

  16. Blair JM, et al. Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis. Nat Clin Pract Oncol. 2006;3(1):41–9.

    Article  CAS  PubMed  Google Scholar 

  17. Rabbani SA, et al. Over-production of parathyroid hormone-related peptide results in increased osteolytic skeletal metastasis by prostate cancer cells in vivo. Int J Cancer. 1999;80(2):257–64.

    Article  CAS  PubMed  Google Scholar 

  18. Orr FW, et al. Tumor-bone interactions in skeletal metastasis. Clin Orthop Relat Res. 1995;312:19–33.

    Google Scholar 

  19. Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. 2002;30(1):5–7.

    Article  CAS  PubMed  Google Scholar 

  20. Parfitt AM. Bone remodeling, normal and abnormal: a biological basis for the understanding of cancer-related bone disease and its treatment. Can J Oncol. 1995;5(Suppl 1):1–10.

    PubMed  Google Scholar 

  21. Raisz LG. Physiology and pathophysiology of bone remodeling. Clin Chem. 1999;45(8 Pt 2):1353–8.

    CAS  PubMed  Google Scholar 

  22. Powell GJ, et al. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res. 1991;51(11):3059–61.

    CAS  PubMed  Google Scholar 

  23. Mantyh PW, et al. Molecular mechanisms of cancer pain. Nat Rev Cancer. 2002;2(3):201–9.

    Article  CAS  PubMed  Google Scholar 

  24. Pareek TK, et al. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci USA. 2007;104(2):660–5.

    Article  CAS  PubMed  Google Scholar 

  25. Sabino MA, et al. Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. Cancer Res. 2002;62(24):7343–9.

    CAS  PubMed  Google Scholar 

  26. Heidenreich A, Ohlmann CH. Ibandronate: its pharmacology and clinical efficacy in the management of tumor-induced hypercalcemia and metastatic bone disease. Expert Rev Anticancer Ther. 2004;4(6):991–1005.

    Article  CAS  PubMed  Google Scholar 

  27. Heidenreich A, Hofmann R, Engelmann UH. The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer. J Urol. 2001;165(1):136–40.

    Article  CAS  PubMed  Google Scholar 

  28. Honore P, et al. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med. 2000;6(5):521–8.

    Article  CAS  PubMed  Google Scholar 

  29. Russell RG. Bisphosphonates: from bench to bedside. Ann N Y Acad Sci. 2006;1068:367–401.

    Article  CAS  PubMed  Google Scholar 

  30. Vitte C, Fleisch H, Guenther HL. Bisphosphonates induce osteoblasts to secrete an inhibitor of osteoclast-mediated resorption. Endocrinology. 1996;137(6):2324–33.

    Article  CAS  PubMed  Google Scholar 

  31. Finley RS. Bisphosphonates in the treatment of bone metastases. Semin Oncol. 2002;29(1 Suppl 4):132–8.

    Article  CAS  PubMed  Google Scholar 

  32. Liu J, et al. Bisphosphonates in the treatment of patients with metastatic breast, lung, and prostate cancer: a meta-analysis. Medicine (Baltimore). 2015;94(46):e2014.

    Article  CAS  Google Scholar 

  33. Van Acker HH, et al. Bisphosphonates for cancer treatment: mechanisms of action and lessons from clinical trials. Pharmacol Ther. 2016;158:24–40.

    Article  CAS  PubMed  Google Scholar 

  34. Berenson JR, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer. 2001;91(7):1191–200.

    Article  CAS  PubMed  Google Scholar 

  35. Strobl S, et al. Adjuvant bisphosphonates and breast cancer survival. Annu Rev Med. 2016;67:1–10.

    Article  CAS  PubMed  Google Scholar 

  36. Rennert G, et al. Oral bisphosphonates and improved survival of breast cancer. Clin Cancer Res. 2017;23(7):1684–89.

    Google Scholar 

  37. Lebret T, et al. The use of bisphosphonates in the management of bone involvement from solid tumours and haematological malignancies – A European survey. Eur J Cancer Care (Engl). 2017 Jul;26(4). doi: 10.1111/ecc.12490.

    Google Scholar 

  38. Hendriks LE, et al. Effect of bisphosphonates, denosumab, and radioisotopes on bone pain and quality of life in patients with non-small cell lung cancer and bone metastases: a systematic review. J Thorac Oncol. 2016;11(2):155–73.

    Article  PubMed  Google Scholar 

  39. Saad F. The role of bisphosphonates in the management of prostate cancer. Curr Oncol Rep. 2006;8(3):221–7.

    Article  CAS  PubMed  Google Scholar 

  40. Berry S, et al. The use of bisphosphonates in men with hormone-refractory prostate cancer: a systematic review of randomized trials. Can J Urol. 2006;13(4):3180–8.

    PubMed  Google Scholar 

  41. Smith MR, et al. Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events. Ann Oncol. 2015;26(2):368–74.

    Article  CAS  PubMed  Google Scholar 

  42. Smith MR, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fizazi K, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gartrell BA, et al. Toxicities following treatment with bisphosphonates and receptor activator of nuclear factor-kappaB ligand inhibitors in patients with advanced prostate cancer. Eur Urol. 2014;65(2):278–86.

    Article  CAS  PubMed  Google Scholar 

  45. Cookson MS, et al. Castration-resistant prostate cancer: AUA guideline amendment. J Urol. 2015;193(2):491–9.

    Article  PubMed  Google Scholar 

  46. Sze WM, et al. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy – A systematic review of randomised trials. Clin Oncol (R Coll Radiol). 2003;15(6):345–52.

    Article  CAS  Google Scholar 

  47. Chow E, et al. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol. 2007;25(11):1423–36.

    Article  PubMed  Google Scholar 

  48. Jeremic B, et al. A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int J Radiat Oncol Biol Phys. 1998;42(1):161–7.

    Article  CAS  PubMed  Google Scholar 

  49. Lo, S.S et al. Expert panel on Radiation Oncology Bone metastases et al. ACR appropriateness criteria. (R) spinal bone metastases. J Palliat Med. 2013;16(1):9–19.

    Google Scholar 

  50. Gaultney J, et al. Results of a dutch cost-effectiveness model of radium-223 in comparison to cabazitaxel, abiraterone, and enzalutamide in patients with metastatic castration resistant prostate cancer previously treated with docetaxel. Value Health. 2015;18(7):A459.

    Article  CAS  PubMed  Google Scholar 

  51. Macedo A, et al. Cost-effectiveness of samarium-153-EDTMP for the treatment of pain due to multiple bone metastases in hormone-refractory prostate cancer versus conventional pain therapy, in Portugal. Acta Medica Port. 2006;19(5):421–6.

    CAS  Google Scholar 

  52. McEwan AJ, et al. A retrospective analysis of the cost effectiveness of treatment with Metastron (89Sr-chloride) in patients with prostate cancer metastatic to bone. Nucl Med Commun. 1994;15(7):499–504.

    Article  CAS  PubMed  Google Scholar 

  53. Silberstein EB. Dosage and response in radiopharmaceutical therapy of painful osseous metastases. J Nucl Med. 1996;37(2):249–52.

    CAS  PubMed  Google Scholar 

  54. Silberstein EB, Elgazzar AH, Kapilivsky A. Phosphorus-32 radiopharmaceuticals for the treatment of painful osseous metastases. Semin Nucl Med. 1992;22(1):17–27.

    Article  CAS  PubMed  Google Scholar 

  55. Lawrence JH, Low-Beer BV, Carpender JW. Chronic lymphatic leukemia; a study of 100 patients treated with radioactive phosphorus. J Am Med Assoc. 1949;140(7):585–8.

    Article  CAS  PubMed  Google Scholar 

  56. Lawrence JH, Dobson RL, et al. Chronic myelogenous leukemia; a study of 129 cases in which treatment was with radioactive phosphorus. J Am Med Assoc. 1948;136(10):672–7.

    Article  CAS  PubMed  Google Scholar 

  57. Maxfield Jr JR, et al. The use of radioactive phosphorus and testosterone in metastatic bone lesions from breast and prostate. South Med J. 1958;51(3):320–7.

    Article  PubMed  Google Scholar 

  58. Cheung A, et al. Evaluation of radioactive phosphorus in the palliation of metastatic bone lesions from carcinoma of the breast and prostate. Radiology. 1980;134(1):209–12.

    Article  CAS  PubMed  Google Scholar 

  59. Silberstein EB. The treatment of painful osseous metastases with phosphorus-32-labeled phosphates. Semin Oncol. 1993;20(3 Suppl 2):10–21.

    CAS  PubMed  Google Scholar 

  60. Blake GM, et al. Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. Eur J Nucl Med. 1986;12(9):447–54.

    Article  CAS  PubMed  Google Scholar 

  61. Laing AH, et al. Strontium-89 chloride for pain palliation in prostatic skeletal malignancy. Br J Radiol. 1991;64(765):816–22.

    Article  CAS  PubMed  Google Scholar 

  62. Silberstein EB, et al. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med. 1985;26(4):345–8.

    CAS  PubMed  Google Scholar 

  63. McEwan AJ. Unsealed source therapy of painful bone metastases: an update. Semin Nucl Med. 1997;27(2):165–82.

    Article  CAS  PubMed  Google Scholar 

  64. Baumrucker S. Palliation of painful bone metastases: Strontium-89. Am J Hosp Palliat Care. 1998;15(2):113–5.

    Article  CAS  PubMed  Google Scholar 

  65. 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(3):238–42.

    Article  CAS  PubMed  Google Scholar 

  66. Blake GM, et al. Strontium-89 therapy: measurement of absorbed dose to skeletal metastases. J Nucl Med. 1988;29(4):549–57.

    CAS  PubMed  Google Scholar 

  67. McEwan AJ. Use of radionuclides for the palliation of bone metastases. Semin Radiat Oncol. 2000;10(2):103–14.

    Article  CAS  PubMed  Google Scholar 

  68. Lewington VJ, et al. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer. 1991;27(8):954–8.

    Article  CAS  PubMed  Google Scholar 

  69. Sciuto R, et al. Radiosensitization with low-dose carboplatin enhances pain palliation in radioisotope therapy with strontium-89. Nucl Med Commun. 1996;17(9):799–804.

    Article  CAS  PubMed  Google Scholar 

  70. Tu SM, et al. Strontium-89 combined with doxorubicin in the treatment of patients with androgen-independent prostate cancer. Urol Oncol. 1996;2(6):191–7.

    Article  CAS  PubMed  Google Scholar 

  71. Giammarile F, et al. Bone pain palliation with 85SR therapy. J Nucl Med. 1999;40(4):585–90.

    CAS  PubMed  Google Scholar 

  72. Fuster D, et al. Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients. Nucl Med Commun. 2000;21(7):623–6.

    Article  CAS  PubMed  Google Scholar 

  73. Jager PL, et al. Treatment with radioactive 89strontium for patients with bone metastases from prostate cancer. BJU Int. 2000;86(8):929–34.

    Article  CAS  PubMed  Google Scholar 

  74. Kraeber-Bodere F, 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(10):1487–93.

    Article  CAS  PubMed  Google Scholar 

  75. Giammarile F, et al. Bone pain palliation with strontium-89 in cancer patients with bone metastases. Q J Nucl Med. 2001;45(1):78–83.

    CAS  PubMed  Google Scholar 

  76. 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(3):219–27.

    CAS  Google Scholar 

  77. Kasalicky J, Krajska V. The effect of repeated strontium-89 chloride therapy on bone pain palliation in patients with skeletal cancer metastases. Eur J Nucl Med. 1998;25(10):1362–7.

    Article  CAS  PubMed  Google Scholar 

  78. Quilty PM, et al. A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer. Radiother Oncol. 1994;31(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  79. Porter AT, McEwan AJ. Strontium-89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial. Semin Oncol. 1993;20(3 Suppl 2):38–43.

    CAS  PubMed  Google Scholar 

  80. Sciuto R, et al. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med. 2002;43(1):79–86.

    CAS  PubMed  Google Scholar 

  81. Akerley W, et al. A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer. 2002;94(6):1654–60.

    Article  CAS  PubMed  Google Scholar 

  82. Tu SM, et al. Therapy tolerance in selected patients with androgen-independent prostate cancer following strontium-89 combined with chemotherapy. J Clin Oncol. 2005;23(31):7904–10.

    Article  CAS  PubMed  Google Scholar 

  83. Tu SM, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001;357(9253):336–41.

    Article  CAS  PubMed  Google Scholar 

  84. Kuroda I, et al. Strontium-89 for prostate cancer with bone metastases: the potential of cancer control and improvement of overall survival. Ann Nucl Med. 2014;28(1):11–6.

    Article  CAS  PubMed  Google Scholar 

  85. Zyskowski A, et al. Strontium-89 treatment for prostate cancer bone metastases: does a prostate-specific antigen response predict for improved survival? Australas Radiol. 2001;45(1):39–42.

    Article  CAS  PubMed  Google Scholar 

  86. Amato RJ, et al. 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(6):532–8.

    Article  CAS  PubMed  Google Scholar 

  87. James ND, et al. Clinical outcomes and survival following treatment of metastatic castrate-refractory prostate cancer with docetaxel alone or with strontium-89, zoledronic acid, or both: the TRAPEZE randomized clinical trial. JAMA Oncol. 2016;2(4):493–9.

    Article  PubMed  Google Scholar 

  88. Heianna J, et al. Concurrent use of strontium-89 with external beam radiotherapy for multiple bone metastases: early experience. Ann Nucl Med. 2015;29(10):848–53.

    Article  CAS  PubMed  Google Scholar 

  89. Bilen MA, et al. Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer. Cancer. 2015;121(1):69–76.

    Article  CAS  PubMed  Google Scholar 

  90. Sciuto R, et al. Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients. Breast Cancer Res Treat. 2001;66(2):101–9.

    Article  CAS  PubMed  Google Scholar 

  91. Pons F, et al. Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer. Eur J Nucl Med. 1997;24(10):1210–4.

    Article  CAS  PubMed  Google Scholar 

  92. Baziotis N, et al. Strontium-89 chloride in the treatment of bone metastases from breast cancer. Oncology. 1998;55(5):377–81.

    Article  CAS  PubMed  Google Scholar 

  93. Heianna J, et al. Tumor regression of multiple bone metastases from breast cancer after administration of strontium-89 chloride (Metastron). Acta Radiol Short Rep. 2014;3(4):2047981613493412.

    PubMed  PubMed Central  Google Scholar 

  94. Zenda S, et al. Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with multiple bone metastases. Int J Clin Oncol. 2014;19(4):739–43.

    Article  CAS  PubMed  Google Scholar 

  95. Maeda O, et al. A patient with esophageal cancer with bone metastasis who achieved pain relief with repetitive administration of strontium-89 chloride. Clin J Gastroenterol. 2014;7(5):387–91.

    Article  PubMed  Google Scholar 

  96. McEwan AJ, et al. A retrospective analysis of the cost effectiveness of treatment with Metastron in patients with prostate cancer metastatic to bone. Eur Urol. 1994;26(Suppl 1):26–31.

    Article  PubMed  Google Scholar 

  97. James N, et al. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer. Health Technol Assess. 2016;20(53):1–288.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Andronis L, et al. Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747). BJU Int. 2017;119(4):522–9.

    Google Scholar 

  99. Singh A, et al. Human pharmacokinetics of samarium-153 EDTMP in metastatic cancer. J Nucl Med. 1989;30(11):1814–8.

    CAS  PubMed  Google Scholar 

  100. Eary JF, et al. Samarium-153-EDTMP biodistribution and dosimetry estimation. J Nucl Med. 1993;34(7):1031–6.

    CAS  PubMed  Google Scholar 

  101. Farhanghi M, 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(8):1451–8.

    CAS  PubMed  Google Scholar 

  102. Collins C, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J Nucl Med. 1993;34(11):1839–44.

    CAS  PubMed  Google Scholar 

  103. Sartor O. Overview of samarium Sm 153 lexidronam in the treatment of painful metastatic bone disease. Rev Urol. 2004;6(Suppl 10):S3–S12.

    PubMed  PubMed Central  Google Scholar 

  104. Serafini AN, 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(4):1574–81.

    Article  CAS  PubMed  Google Scholar 

  105. Resche I, et al. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997;33(10):1583–91.

    Article  CAS  PubMed  Google Scholar 

  106. Sartor O, et al. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004;63(5):940–5.

    Article  PubMed  Google Scholar 

  107. Wang RF, 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(2):97–101.

    Article  PubMed  Google Scholar 

  108. Marcus CS, et al. Lack of effect of a bisphosphonate (pamidronate disodium) infusion on subsequent skeletal uptake of Sm-153 EDTMP. Clin Nucl Med. 2002;27(6):427–30.

    Article  PubMed  Google Scholar 

  109. Turner JH, et al. A phase II study of treatment of painful multifocal skeletal metastases with single and repeated dose samarium-153 ethylenediaminetetramethylene phosphonate. Eur J Cancer. 1991;27(9):1084–6.

    Article  CAS  PubMed  Google Scholar 

  110. Turner JH, et al. A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases. J Clin Oncol. 1989;7(12):1926–31.

    Article  CAS  PubMed  Google Scholar 

  111. Sartor O, et al. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer. 2007;109(3):637–43.

    Article  CAS  PubMed  Google Scholar 

  112. Suttmann H, et al. Combining Sm-153-lexidronam and docetaxel for the treatment of patients with hormone-refractory prostate cancer: first experience. Cancer Biother Radiopharm. 2008;23(5):609–18.

    Article  CAS  PubMed  Google Scholar 

  113. Morris MJ, et al. Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer. J Clin Oncol. 2009;27(15):2436–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Autio KA, et al. Repetitively dosed docetaxel and 153samarium-EDTMP as an antitumor strategy for metastatic castration-resistant prostate cancer. Cancer. 2013;119(17):3186–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Tu SM, et al. Phase I study of concurrent weekly docetaxel and repeated samarium-153 lexidronam in patients with castration-resistant metastatic prostate cancer. J Clin Oncol. 2009;27(20):3319–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Fizazi K, et al. Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer. J Clin Oncol. 2009;27(15):2429–35.

    Article  CAS  PubMed  Google Scholar 

  117. Lin J, et al. Phase I trial with a combination of docetaxel and 153Sm-lexidronam in patients with castration-resistant metastatic prostate cancer. Urol Oncol. 2011;29(6):670–5.

    Article  CAS  PubMed  Google Scholar 

  118. Barai S, et al. Effects of low-dose capecitabine on Samarium-153-EDTMP therapy for painful bone metastases. Indian J Nucl Med. 2015;30(2):111–5.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Winderen M, et al. Pronounced therapeutic effect of samarium 153-ethylenediaminetetramethylene phosphonate in an orthotopic human osteosarcoma tibial tumor model. J Natl Cancer Inst. 1995;87(3):221–2.

    Article  CAS  PubMed  Google Scholar 

  120. Franzius C, et al. High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma. Nuklearmedizin. 2001;40(6):215–20.

    CAS  PubMed  Google Scholar 

  121. Franzius C, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol. 2002;20(7):1953–4.

    Article  PubMed  Google Scholar 

  122. Anderson PM, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol. 2002;20(1):189–96.

    Article  CAS  PubMed  Google Scholar 

  123. Anderson PM, et al. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. Clin Cancer Res. 2005;11(19 Pt 1):6895–900.

    Article  CAS  PubMed  Google Scholar 

  124. Henriksen G, et al. Ra-223 for endoradiotherapeutic applications prepared from an immobilized Ac-227/Th-227 source. Radiochim Acta. 2001;89(10):661–6.

    Article  CAS  Google Scholar 

  125. Biersack HJ, et al. Radium-223 in prostate cancer. N Engl J Med. 2013;369(17):1659.

    Article  CAS  PubMed  Google Scholar 

  126. Henriksen G, et al. Significant antitumor effect from bone-seeking, alpha-particle-emitting 223Ra demonstrated in an experimental skeletal metastases model. Cancer Res. 2002;62(11):3120–5.

    CAS  PubMed  Google Scholar 

  127. Nilsson S, et al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11(12):4451–9.

    Article  CAS  PubMed  Google Scholar 

  128. Carrasquillo JA, 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(9):1384–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Kairemo K, et al. Evaluation of alpha-therapy with radium-223-dichloride in castration resistant metastatic prostate cancer-the role of gamma scintigraphy in dosimetry and pharmacokinetics. Diagnostics (Basel). 2015;5(3):358–68.

    Article  Google Scholar 

  130. Nilsson S, et al. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007;8(7):587–94.

    Article  CAS  PubMed  Google Scholar 

  131. Nilsson S, et al. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin Genitourin Cancer. 2013;11(1):20–6.

    Article  PubMed  Google Scholar 

  132. Parker C, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23.

    Article  CAS  PubMed  Google Scholar 

  133. Vogelzang NJ, et al. Hematologic safety of radium-223 dichloride: baseline prognostic factors associated with myelosuppression in the ALSYMPCA trial. Clin Genitourin Cancer. 2017;15(1):42–52.

    Google Scholar 

  134. Saad F, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016;17(9):1306–16.

    Article  CAS  PubMed  Google Scholar 

  135. Sartor O, et al. Chemotherapy following radium-223 dichloride treatment in ALSYMPCA. Prostate. 2016;76(10):905–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Shore ND, et al. Interim results from ERADICATE: an open-label phase 2 study of radium Ra 223 dichloride with concurrent administration of abiraterone acetate plus prednisone in castration-resistant prostate cancer subjects with symptomatic bone metastases. Clin Adv Hematol Oncol. 2016;14(4 Suppl 5):3–7.

    Google Scholar 

  137. Suominen MI, et al. Survival benefit with radium-223 dichloride in a mouse model of breast cancer bone metastasis. J Natl Cancer Inst. 2013;105(12):908–16.

    Article  PubMed  Google Scholar 

  138. Coleman R, 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(2):411–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. de Klerk JM, et al. Phase 1 study of rhenium-186-HEDP in patients with bone metastases originating from breast cancer. J Nucl Med. 1996;37(2):244–9.

    PubMed  Google Scholar 

  140. Zafeirakis A, et al. Management of metastatic bone pain with repeated doses of rhenium 186-HEDP in patients under therapy with zoledronic acid: a safe and additively effective practice. Cancer Biother Radiopharm. 2009;24(5):543–50.

    Article  CAS  PubMed  Google Scholar 

  141. van der Poel HG, et al. Serum hemoglobin levels predict response to strontium-89 and rhenium-186-HEDP radionuclide treatment for painful osseous metastases in prostate cancer. Urol Int. 2006;77(1):50–6.

    Article  PubMed  CAS  Google Scholar 

  142. O’Sullivan JM, et al. High activity rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone. Br J Cancer. 2002;86(11):1715–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Lange R, et al. Applying quality by design principles to the small-scale preparation of the bone-targeting therapeutic radiopharmaceutical rhenium-188-HEDP. Eur J Pharm Sci. 2016;90:96–101.

    Article  CAS  PubMed  Google Scholar 

  144. ter Heine R, et al. Bench to bedside development of GMP grade rhenium-188-HEDP, a radiopharmaceutical for targeted treatment of painful bone metastases. Int J Pharm. 2014;465(1–2):317–24.

    Article  PubMed  CAS  Google Scholar 

  145. Liepe K, et al. Dosimetry of 188Re-hydroxyethylidene diphosphonate in human prostate cancer skeletal metastases. J Nucl Med. 2003;44(6):953–60.

    CAS  PubMed  Google Scholar 

  146. Palmedo H, et al. Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med. 2000;27(2):123–30.

    Article  CAS  PubMed  Google Scholar 

  147. Liepe K, Runge R, Kotzerke J. Systemic radionuclide therapy in pain palliation. Am J Hosp Palliat Care. 2005;22(6):457–64.

    Article  PubMed  Google Scholar 

  148. Palmedo H, 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(15):2869–75.

    Article  CAS  PubMed  Google Scholar 

  149. Lange R, et al. Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Clinical benefit in a real-world study. Nuklearmedizin. 2016;55(5):188–95.

    Article  PubMed  Google Scholar 

  150. Krishnamurthy GT, et al. Tin-117m(4+)DTPA: pharmacokinetics and imaging characteristics in patients with metastatic bone pain. J Nucl Med. 1997;38(2):230–7.

    CAS  PubMed  Google Scholar 

  151. Srivastava SC, et al. Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study. Clin Cancer Res. 1998;4(1):61–8.

    CAS  PubMed  Google Scholar 

  152. Ando A, et al. 177Lu-EDTMP: a potential therapeutic bone agent. Nucl Med Commun. 1998;19(6):587–91.

    Article  CAS  PubMed  Google Scholar 

  153. Chakraborty S, et al. 177Lu labelled polyaminophosphonates as potential agents for bone pain palliation. Nucl Med Commun. 2002;23(1):67–74.

    Article  CAS  PubMed  Google Scholar 

  154. Das T, et al. 177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation. Appl Radiat Isot. 2002;57(2):177–84.

    Article  CAS  PubMed  Google Scholar 

  155. Chakraborty S, et al. 177Lu-EDTMP: a viable bone pain palliative in skeletal metastasis. Cancer Biother Radiopharm. 2008;23(2):202–13.

    Article  CAS  PubMed  Google Scholar 

  156. Yuan J, et al. 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;38(2):88–92.

    Article  PubMed  Google Scholar 

  157. Thapa P, et al. Clinical efficacy and safety comparison of 177Lu-EDTMP with 153Sm-EDTMP on an equidose basis in patients with painful skeletal metastases. J Nucl Med. 2015;56(10):1513–9.

    Article  CAS  PubMed  Google Scholar 

  158. Guideline. Medical use of byproduct material. Title 10, code of federal regulations. http://www.rc.gov/reading-rm/doccollections/cfr/part035/part035-0075.html.

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Neeta Pandit-Taskar

  2. Department of Radiology, Weill Cornell Medical College, 1275 York Avenue, New York, NY, 10065, USA

    Neeta Pandit-Taskar

  3. Jenkintown, PA, USA

    Chaitanya R. Divgi

Authors
  1. Neeta Pandit-Taskar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chaitanya R. Divgi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neeta Pandit-Taskar .

Editor information

Editors and Affiliations

  1. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    H. William Strauss

  2. University of Pisa, Regional Center of Nuclear Medicine, Pisa, Italy

    Giuliano Mariani

  3. University of Pisa, Regional Center of Nuclear Medicine, Pisa, Italy

    Duccio Volterrani

  4. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Steven M. Larson

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Pandit-Taskar, N., Divgi, C.R. (2017). Targeted Radionuclide Therapy for Bone Metastasis. In: Strauss, H., Mariani, G., Volterrani, D., Larson, S. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-26236-9_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26236-9_27

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26234-5

  • Online ISBN: 978-3-319-26236-9

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation