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The Bone Pathway: 223Ra-Dichloride

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Radiopharmaceuticals

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Abstract

Several beta-emitting radiopharmaceuticals, including 89Sr-chloride, 186Re-hydroxyethylidene diphosphonate, and 153Sm-ethylene diamine tetramethylene phosphonate, have been developed for palliation of bone pain due to metastases. 223Ra dichloride is a novel bone-seeking alpha emitter used for treatment of CRPC in patients with bone metastases. It is a calcium-mimetic solution that selectively targets area of increased bone turnover in bone metastases. First clinical studies with 223Ra started in 2012. This chapter aims to describe the employment of 223Ra-dichloride in clinical setting, by analyzing the different clinical trials and future perspectives for this targeted nuclear medicine therapy.

The authors declared that they have obtained the permission for any previously published material used in the chapter.

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Abbreviations

153Sm:

Samarium-153

186Re:

Rhenium-186

223Ra:

Radium-223

89Sr:

Strontium-89

ALARA:

As low as reasonably achievable

ALP:

Alkalinephosphate

ALSYMPCA:

ALpharadin in SYMPtomatic Prostate CAncer

CRPC:

Castrate-resistant prostate cancer

CT:

Computed tomography

EBRT:

External beam radiotherapy

Gy:

Gray

LET:

Linear energy transfer

MBq:

MegaBequerel

MDP:

Methyl disphosphonate

Mev:

Megaelectronvolt

mSv:

Milli-sievert

NIST:

National Institute of Standard and Technology

PET:

Positron emission tomography

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  Google Scholar 

  2. Carrasquillo JA, O’Donoghue JA, Pandit-Taskar N. 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. 2003;40:1384–93.

    Article  Google Scholar 

  3. Nilsson S, Franzén L, Parker C, 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  CAS  Google Scholar 

  4. Nilsson SL, Larsen RH, Foss SD, et al. First clinical experience with a-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11:4451–9.

    Article  CAS  Google Scholar 

  5. Nilsson S, Strang P, Aksnes A, et al. A randomized, dose-response, multicentre phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer. 2012;48:678–86.

    Article  CAS  Google Scholar 

  6. Parker C, Pascoe S, Chodacki A, et al. A randomized. Double-blind, dose-finding, multicenter phase 2 trial or radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol. 2013;63(2):189–97.

    Article  CAS  Google Scholar 

  7. Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014;15:738–46.

    Article  CAS  Google Scholar 

  8. Pacilio M, Ventroni G, Cassano B, et al. A case report of image-based dosimetry of bone metastases with Alpharadin (223Ra-dichloride) therapy: inter-fraction variability of absorbed dose and follow-up. Ann Nucl Med. 2016;30:163–8.

    Article  Google Scholar 

  9. Pacilio M, Ventroni G, De Vincentis G, et al. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223Ra-dichloride. Eur J Nucl Med Mol Imaging. 2016;43(1):21–33.

    Article  CAS  Google Scholar 

  10. Hindorf C, Chittenden S, Aksnes A-K, et al. Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl Med Commun. 2012;33:726–32.

    Article  CAS  Google Scholar 

  11. AIFM-AIMN. Linee guida AIFM-AIMN per l’utilizzo terapeutico del 223-Ra. 2014.

    Google Scholar 

  12. Stabin S a. Health Phys. 2012;102:271–91.

    Article  Google Scholar 

  13. Nilsson S, Balteskard L, Foss SD, et al. Phase I study of Alpharadin2 (223Ra), and a-emitting bone-seeking agent in cancer patients with skeletalmetastases. Eur J Nucl Med Mol Imaging. 2004;31:S290/no 370 [abstract].

    Google Scholar 

  14. Carrasquillo JA, J. A. O’Donoghue, Pandit-Taskar N, et al. Phase I pharmacokinetic (PK) and biodistribution study of radium-223 chloride in patients with castration resistant prostate cancer (CRPC) metastatic to bone. 46th annu Meet am Soc Clin oncol (aSCo) (June 4–8, Chicago) 2010, abstratc 4680. 2010.

    Google Scholar 

  15. Chittenden S, Hindorf C, Parker C, et al. A phase 1, open-label study of the biodistribution, pharmacokinetics, and dosimetry of 223Ra-dichloride in patients with hormone-refractory prostate cancer and skeletal metastases. J Nucl Med. 2015;56:1304–9.

    Article  CAS  Google Scholar 

  16. 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  CAS  Google Scholar 

  17. Pacilio M, Cassano B, et al. Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases. Phys Med. 2017 Sep;41:117–23. https://doi.org/10.1016/j.ejmp.2017.04.019.

    Article  PubMed  Google Scholar 

  18. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  Google Scholar 

  19. Vogelzang NJ, Coleman RE, Michalski JM, 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.e8.

    Article  Google Scholar 

  20. Saad F, Carles J, Gillessen S, 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;17:1306–16.

    Article  CAS  Google Scholar 

  21. Sartor AO, Heinrich D., Mariados N, et al. Radium-223 (Ra-223) re-treatment (Re-tx): first experience from an international, multicenter, prospective study in patients (Pts) with castration-resistant prostate cancer and bone metastases (mCRPC). Genitourinary Cancers Symposium 2016. 2016.

    Google Scholar 

  22. Morris MJ, HJ Hammers, Sweeney C, et al. Safety of radium-223 dichloride (Ra-223) with docetaxel (D) in patients with bone metastases from castration-resistant prostate cancer (CRPC): a phase I prostate Cancer clinical trials consortium study. ASCO Annual Meeting 2013. 2013.

    Google Scholar 

  23. Wilson JM, Parker C. The safety and efficacy of radium-223 dichloride for the treatment of advanced prostate cancer. Expert Rev Anticancer Ther. 2016;16:911–8.

    Article  CAS  Google Scholar 

  24. Dalla Volta A, Formenti A, Berruti A. Higher risk of fragility fractures in prostate cancer patients treated with combined radium-223 and abiraterone: prednisone may be the culprit. Eur Urol. 2019;75(6):894–5. https://doi.org/10.1016/j.eururo.2019.01.026.

    Article  PubMed  Google Scholar 

  25. Dizdarevic S, Petersen PM, Essler M, Versari A, Bourre J-C, la Fougere C, et al. Interim analysis of the REASSURE (Radium-223 alpha emitter agent in non-intervetional safety study in mCRPC population for long-term evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice. Eur J Nucl Med Mol Imaging. 2019;46:1102. https://doi.org/10.1007/s00259-019-4261-y.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Evangelista L, Zorz A. Re: response assessment of 223Ra treatment: should a fluorocholine PET/CT be performed? Clin Nucl Med. 2018;43(11):867–8.

    PubMed  Google Scholar 

  27. García Vicente AM, Soriano Castrejón Á, Alvarez Cabellos R, Sanchez Gil B, Mohedano Mohedano N. Response assessment of 223Ra treatment: should a fluorocholine PET/CT be performed? Clin Nucl Med. 2017;42(10):761–5.

    Article  Google Scholar 

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Authors and Affiliations

  1. Nuclear Medicine Unit, Veneto Institute of Oncology IOV—IRCCS, Padua, Italy

    Laura Evangelista

  2. Medical Physic Unit, Veneto Institute of Oncology IOV—IRCCS, Padua, Italy

    Alessandra Zorz

Authors
  1. Laura Evangelista
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  2. Alessandra Zorz
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Corresponding author

Correspondence to Laura Evangelista .

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Editors and Affiliations

  1. Department of Nuclear Medicine and Theranostics, Mariano Santo Hospital, Cosenza, Italy

    Ferdinando Calabria

  2. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

    Orazio Schillaci

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Evangelista, L., Zorz, A. (2020). The Bone Pathway: 223Ra-Dichloride. In: Calabria, F., Schillaci, O. (eds) Radiopharmaceuticals. Springer, Cham. https://doi.org/10.1007/978-3-030-27779-6_10

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  • DOI: https://doi.org/10.1007/978-3-030-27779-6_10

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-27778-9

  • Online ISBN: 978-3-030-27779-6

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