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Therapeutic Nuclear Medicine pp 447–457Cite as

Treatment of Osteoblastic Skeletal Metastases by the Alpha-Emitting Bone-Seeker Radium-223

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Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

Radium-223 dichloride selectively targets osteoblastic bone metastases with high-energy, short-range alpha-particles following intravenous injection. It is the first targeted alpha-emitter to improve overall survival in randomized phase 2 and 3 studies and provides a novel treatment option with favorable safety profile in castrate-resistant prostate cancer patients with bone metastases.

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References

  • Anderson RM, Stevens DL, Sumption ND et al (2007) Effect of linear energy transfer (LET) on the complexity of alpha-particle induced chromosome aberrations in human CD341 cells. Radiat Res 167:541–550

    Article  PubMed  Google Scholar 

  • Barnes EA (2011) Radiopharmaceuticals for painful bone metastases: perspective from radiation oncology. J Support Oncol 9(6):208–209

    Article  CAS  PubMed  Google Scholar 

  • British Association of Surgical Oncology (1999) The management of metastatic bone disease in the United Kingdom. Eur J Surg Onc 25:3–23

    Article  Google Scholar 

  • Bruland OS, Hird A, Chow E (2008a) Radiotherapy of skeletal metastases. In: ASBMR-primer, Chapter 86, 7th edn. American Society for Bone and Mineral Research, USA, pp 404–407

    Google Scholar 

  • Bruland OS, Jonasdottir TJ, Fisher DR, Larsen RH (2008b) Radium-223: from radiochemical development to clinical applications in targeted cancer therapy. Curr Radiopharm 1:203–208

    Article  CAS  Google Scholar 

  • Bruland ØS, Nilsson S, Fisher DR, Larsen RH (2006) High linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res 12:6250s–6257s

    Article  CAS  PubMed  Google Scholar 

  • Casimiro S, Guise TA, Chirgwin J (2009) The critical role of the bone microenvironment in cancer metastases. Mol Cell Endocrinol 310:71–81

    Article  CAS  PubMed  Google Scholar 

  • Chung LW (2003) Prostate carcinoma bone-stroma interaction and its biologic and therapeutic implications. Cancer 97:772–778

    Article  PubMed  Google Scholar 

  • Cook G Jr, Parker C, Chua S, Johnson B, Aksnes AK, Lewington VJ (2011a) 18F-fluoride PET: changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with 223Ra-chloride (Alpharadin). EJNMMI Res 1(1):4

    Article  PubMed Central  PubMed  Google Scholar 

  • Cook GJ, Venkitaraman R, Sohaib AS, Lewington VJ, Chua SC, Huddart RA, Parker CC, Dearnaley DD, Horwich A (2011b) The diagnostic utility of the flare phenomenon on bone scintigraphy in staging prostate cancer. Eur J Nucl Med Mol Imaging 38(1):7–13

    Article  PubMed  Google Scholar 

  • Cooper CR, Chay CH, Gendernalik JD et al (2003) Stromal factors involved in prostate carcinoma metastasis to bone. Cancer 97:739–747

    Article  PubMed  Google Scholar 

  • Guise TA, Mundy GR (1998) Cancer and bone. Endocr Rev 19:18–54

    CAS  PubMed  Google Scholar 

  • Hage WD (2000) Incidence, location, and diagnostic evaluation of metastatic bone disease. Orthop Clin N Am 31:515–528

    Article  CAS  Google Scholar 

  • Hall EJ (2000) Radiobiology for the radiologist, Chapter 10, 5th edn. Lippincott Williams & Wilkins, Philadelphia, p 153

    Google Scholar 

  • Harvie DI (1999) The radium century. Endeavour 23(3):100–105

    Article  CAS  PubMed  Google Scholar 

  • Henriksen G, Alstad J, Hoff P, Larsen RH (2001) 223Ra for endotherapeutic applications prepared from an immobilized 227Ac/227Th source. Radiochim Acta 89:661–666

    Article  CAS  Google Scholar 

  • Henriksen G, Breistol K, Bruland OS, Fodstad O, Larsen RH (2002) Significant antitumor effect from bone-seeking, alpha-particle-emitting 223Ra demonstrated in an experimental skeletal metastases model. Cancer Res 62:3120–3125

    CAS  PubMed  Google Scholar 

  • Henriksen G, Fisher DR, Roeske JC, Bruland OS, Larsen RH (2003) Targeting of osseous sites with alpha-emitting 223Ra: comparison with the beta-emitter 89Sr in mice. J Nucl Med 44:252–259

    CAS  PubMed  Google Scholar 

  • Hindorf C, Chittenden S, Aksnes AK, Parker C, Flux GD (2012) Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl Med Commun 33(7):726–732

    Article  CAS  PubMed  Google Scholar 

  • http://clinicaltrials.gov/ct2/show/NCT00699751

  • http://www.mskcc.org/mskcc/html/2270.cfm?IRBNO=10-086

  • Kerr C (2002) 223Ra targets skeletal metastases and spares normal tissue. Lancet Oncol 3:453

    Article  PubMed  Google Scholar 

  • Lange P, Vessella R (1999) Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone. Cancer Metastasis Rev 17:331–336

    Article  CAS  Google Scholar 

  • Larsen RH, Saxtorph H, Skydsgaard M, Borrebaek J, Jonasdottir TJ, Bruland OS, Klastrup S, Harling R, Ramdahl T (2006) Radiotoxicity of the alpha-emitting bone-seeker 223Ra injected intravenously into mice: histology, clinical chemistry and hematology. In Vivo 20(3):325–331

    CAS  PubMed  Google Scholar 

  • Lassmann M, Nosske D, Reiners C (2002) Therapy of ankylosing spondylitis with 224Ra-radium chloride: dosimetry and risk considerations. Radiat Environ Biophys 41:173–178

    PubMed  Google Scholar 

  • Lee SE, Min CK, Yahng SA et al (2011) Bone scan images reveal increased osteoblastic function after bortezomib treatment in patients with multiple myeloma. Eur J Haematol 86:83–86

    Article  PubMed  Google Scholar 

  • Lewington VJ (2005) Bone-seeking radionuclides for therapy. J Nucl Med 46(Suppl 1):38S–47S

    CAS  PubMed  Google Scholar 

  • Li Y, Russell PJ, Allen BJ (2004) Targeted alpha-therapy for control of micrometastatic prostate cancer. Expert Rev Anticancer Ther 4:459–468

    Article  CAS  PubMed  Google Scholar 

  • Liepe K (2009) Alpharadin, a 223Ra-based alpha-particle-emitting pharmaceutical for the treatment of bone metastases in patients with cancer. Curr Opin Investig Drugs 10:1346–1358

    CAS  PubMed  Google Scholar 

  • Lin SH, Cheng CJ, Lee YC et al (2008) A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation. Oncogene 27:5195–5203

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lipton A, Berenson JR, Body JJ et al (2006) Advances in treating metastatic bone cancer: summary statement for the first Cambridge conference. Clin Cancer Res 12:6209s–6212s

    Article  PubMed Central  PubMed  Google Scholar 

  • Loberg RD, Logothetis CJ, Keller ET, Pienta KJ (2005) Pathogenesis and treatment of prostate cancer bone metastases: targeting the lethal phenotype. J Clin Oncol 23:8232–8241

    Article  CAS  PubMed  Google Scholar 

  • Macklis RM (2002) Portrait of science. Scientist, technologist, proto-feminist, superstar. Science 295(5560):1647–1648

    Article  CAS  PubMed  Google Scholar 

  • Martland HS, Humphries RE (1929) Osteogenic sarcoma in dial painters using luminous paint. Arch Pathol 7:406–417

    CAS  Google Scholar 

  • Mould RF (1999) Marie and Pierre Curie and radium: history, mystery, and discovery. Med Phys 26(9):1766–1772

    Article  CAS  PubMed  Google Scholar 

  • Mundy GR (2002) Metastasis to bone: causes, consequences, and therapeutic opportunities. Nat Rev Cancer 2:584–593

    Article  CAS  PubMed  Google Scholar 

  • Nekolla EA, Kreisheimer M, Kellerer AM, Kuse IM, Gossner W, Spiess H (2000) Induction of malignant bone tumors in radium-224 patients: risk estimates based on the improved dosimetry. Radiat Res 153:93–103

    Article  CAS  PubMed  Google Scholar 

  • Nielsen OS, Munro AJ, Tannock IF (1991) Bone metastases: pathophysiology and management policy. J Clin Oncol 9:509–524

    CAS  PubMed  Google Scholar 

  • Nilsson S, Balteskard L, Fosså SD et al (2005) First clinical experiences with alpha emitter radium-223 in the treatment of skeletal metastases from breast and prostate cancer. Clin Cancer Res 11:4451–4459

    Article  CAS  PubMed  Google Scholar 

  • Nilsson S, Franzén L, Parker C et al (2007) Bone-targeted radium-223 in symptomatic, hormone refractory prostate cancer: a randomized, placebo-controlled, phase 2 study. Lancet Oncol 8:587–594

    Article  CAS  PubMed  Google Scholar 

  • Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, Lennernäs B, Petersson U, Johannessen DC, Sokal M, Pigott K, O’Bryan-Tear CG, Thuresson M, Bolstad B, Bruland OS (in press) 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

    Google Scholar 

  • Nilsson S, Strang P, Aksnes AK, Franzèn L, Olivier P, Pecking A, Staffurth J, Vasanthan S, Andersson C, Bruland ØS (2012) A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer 48(5):678–686

    Article  CAS  PubMed  Google Scholar 

  • Norris WP, Speckman TW, Gustafson PF (1955) Studies of the metabolism of radium in man. Am J Roentgenol 73:785–802

    CAS  Google Scholar 

  • Paes FM, Ernani V, Hosein P, Serafini AN (2011) Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. J Support Oncol 9(6):197–205

    Article  CAS  PubMed  Google Scholar 

  • Pandit-Taskar N, Batraki M, Divgi CR (2004) Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med 45:1358–1365

    CAS  PubMed  Google Scholar 

  • Parker C, Nilsson S, Heinrich D, et al (2012) Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA). Oral presentation at Annual Meeting of the American Society of Clinical Oncology Abstract LBA4512

    Google Scholar 

  • Parker CC, Pascoe S, Chodacki A, O’Sullivan JM, Germá JR, O’Bryan-Tear CG, Haider T, Hoskin P (2013) A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol 63(2):189–197

    Article  CAS  PubMed  Google Scholar 

  • Ritter MA, Cleaver JE, Tobias CA (1977) High-LET radiations induce a large proportion of non-rejoining DNA breaks. Nature 266:653–655

    Article  CAS  PubMed  Google Scholar 

  • Roudier MP, Morrissey C, True LD et al (2008) Histopathological assessment of prostate cancer bone osteoblastic metastases. J Urol 180:1154–1160

    Article  PubMed Central  PubMed  Google Scholar 

  • Sartor O, Bruland O (2011) Stromal targeted therapies in prostate and renal cancer: new concepts and knowledge. Clin Genitourin Cancer 9(1):1–2

    PubMed  Google Scholar 

  • Sartor O, Goeckeler W, Bruland O (2011) Stromal targeted therapy in bone metastatic prostate cancer: promise delivered. Asian J Androl 13(6):783–784

    Article  PubMed Central  PubMed  Google Scholar 

  • Sartor O, Hoskin P, Bruland OS (2013) Targeted radio-nuclide therapy of skeletal metastases. Cancer Treat Rev 39(1):18–26

    Article  CAS  PubMed  Google Scholar 

  • Shah SK, Ryan CJ, Kilian C et al (2010) Bone scan “flare” in patients receiving abiraterone acetate (AA) for metastatic castration resistant prostate cancer (mCRPC): analysis of data from a phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium. J Clin Oncol 28:15s

    Article  Google Scholar 

  • Sikes RA, Nicholson BE, Koeneman KS et al (2004) Cellular interactions in the tropism of prostate cancer to bone. Int J Cancer 110:497–503

    Article  CAS  PubMed  Google Scholar 

  • Silberstein EB (2000) Systemic radiopharmaceutical therapy of painful osteoblastic metastases. Semin Radiat Oncol 10:240–249

    Article  CAS  PubMed  Google Scholar 

  • Spiess H (2010) Life-span study on late effects of 224Ra in children and adults. Health Phys 99(3):286–291

    Article  CAS  PubMed  Google Scholar 

  • Tiepolt C, Grunning T, Franke WG (2001) Reaissance of 224Ra treatment in ankylosing spondylitis. J Nucl Med 42S:128P

    Google Scholar 

  • Tomblyn M (2012) The role of bone-seeking radionuclides in the palliative treatment of patients with painful osteoblastic skeletal metastases. Cancer Control 19(2):137–144

    CAS  PubMed  Google Scholar 

  • Vogel CL, Schoenfelder J, Shemano I, Hayes DF, Gams RA (1995) Worsening bone scan in the evaluation of antitumor response during hormonal therapy of breast cancer. J Clin Oncol 13:1123–1128

    CAS  PubMed  Google Scholar 

  • Weilbaecher KN, Guise TA, McCauley LK (2011) Cancer to bone: a fatal attraction. Nat Rev Cancer 11:411–425

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wheldon TE, O’Donoghue JA (1990) The radiobiology of targeted radiotherapy. Int J Radiat Biol 58:1–21

    Article  CAS  PubMed  Google Scholar 

  • Wick RR, Atkinson MJ, Nekolla EA (2009) Incidence of leukaemia and other malignant diseases following injections of the short-lived alpha-emitter 224Ra into man. Radiat Environ Biophys 48(3):287–294

    Article  PubMed  Google Scholar 

  • Wick RW, Nekolla EA, Gøssner W, Kellerer AM (1999) Late effects in ankylosing spondylitis patients treated with 224Ra. Radiation Res 152:S8–S11

    Article  CAS  PubMed  Google Scholar 

  • Yates C (2011) Prostate tumor cell plasticity: a consequence of the microenvironment. Adv Exp Med Biol 720:81–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, The Norwegian Radium Hospital, Institute for Clinical Medicine, University of Oslo, Montebello, 0310, Oslo, Norway

    Øyvind S. Bruland

  2. Sciencons Ltd., Kjelsåsveien 168 B, 0884, Oslo, Norway

    Roy H. Larsen

Authors
  1. Øyvind S. Bruland
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  2. Roy H. Larsen
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Corresponding author

Correspondence to Øyvind S. Bruland .

Editor information

Editors and Affiliations

  1. THERANOSTICS Center for Molecular, Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka, Germany

    Richard P. Baum

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Bruland, Ø.S., Larsen, R.H. (2013). Treatment of Osteoblastic Skeletal Metastases by the Alpha-Emitting Bone-Seeker Radium-223. In: Baum, R. (eds) Therapeutic Nuclear Medicine. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2013_819

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  • DOI: https://doi.org/10.1007/174_2013_819

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  • Print ISBN: 978-3-540-36718-5

  • Online ISBN: 978-3-540-36719-2

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