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Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters

Hinrich A Wieder, Michael Lassmann, Martin S Allen-Auerbach, Johannes Czernin, Ken Herrmann
World Journal of Radiology 2014 July 28, 6 (7): 480-5
25071888
Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit β-rays such as (153)Samarium and (89)Strontium and achieve palliation are commercially available. In contrast to β-emitters, (223)Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for (223)Radium which is expressed in a lower myelotoxicity. The α emitter (223)Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the (223)Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in pain palliation and thus, improved quality of life and a delay of skeletal related events. At the same time the toxicity profile of (223)Radium was favourable. Since May 2013, (223)Radium dichloride (Xofigo(®)) is approved by the US Food and Drug Administration.

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