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Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions

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Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone metastases sites to deliver focal cytotoxic levels of radiation emerged as an effective treatment modality for the palliation of symptomatic bone metastases. Bone-seeking radiopharmaceuticals not only provide palliative benefit but also improve clinical outcomes in terms of overall and progression-free survival. There is a steadily expanding list of therapeutic radionuclides that are used or can potentially be used in either ionic form or in combination with carrier molecules for the management of bone metastases. This article offers a narrative review of the armamentarium of bone-targeting radiopharmaceuticals based on currently approved investigational and potentially useful radionuclides and examines their efficacy for the treatment of painful skeletal metastases. In addition, the article also highlights the processes, opportunities, and challenges involved in the development of bone-seeking radiopharmaceuticals. Radium-223 is the first agent in this class to show an overall survival advantage in castration-resistant prostate cancer (CRPC) patients with bone metastases. This review summarizes recent advances, current clinical practice using radiopharmaceuticals for bone pain palliation, and the expected future prospects in this field.
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Keywords: Bisphosphonates; Bone; Cancer; Hydroxyapatite; Metastasis; Pain; Palliation; Radionuclide; Radiopharmaceuticals

Affiliations: 1: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India. 2: Homi Bhabha National Institute, Anushaktinagar, Mumbai-400094, India. 3: Medical Isotopes Program, Isotope Development Group, MS 6229, Bldg. 4501, Oak Ridge National Laboratory, PO Box 2008, 1 Bethel Valley Road, Oak Ridge, TN, 37831, USA.

Appeared or available online: March 15, 2019

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