High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the α-Emitter 223Ra: Adjuvant or Alternative to Conventional Modalities?
Clinical Cancer Research, October 2006
Øyvind S. Bruland, Sten Nilsson, Darrell R. Fisher, Roy H. Larsen
The bone-seeking, alpha-particle-emitting radiopharmaceutical Alpharadin, 223RaCl2 (half-life=11.4 days), is under clinical development as a novel treatment for skeletal metastases from breast and prostate cancer. This article summarizes the current status of preclinical and clinical research on 223RaCl2. Potential advantages of 223Ra to that of external beam irradiation and registered beta-emitting bone seekers are discussed. Published data of 223Ra dosimetry in mice and a therapeutic study in a skeletal metastases model in nude rats have indicated significant therapeutic potential of bone-seeking alpha-emitters. This article provides short-term and long-term results from the first clinical single dosage trial. We also present data from a repeated dosage study of five consecutive injections of 50 kBq/kg body weight, once every 3rd week, or two injections of 125 kBq/kg body weight, 6 weeks apart. Furthermore, interim results are described for a randomized phase 2 trial involving 64 patients with hormone-refractory prostate cancer and painful skeletal metastases who received four monthly injections of 223Ra or saline as an adjuvant to external beam radiotherapy. Lastly, we present preliminary dose estimates for 223Ra in humans. Results indicate that repeated dosing is feasible and toxicity is low, and that opportunities are available for combined treatment strategies.
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