High-linear energy transfer irradiation targeted to skeletal metastases by the α-emitter 223Ra:: Adjuvant or alternative to conventional modalities?

The bone-seeking alpha-particle-emitting radiopharmaceutical Alpharadin, (RaCl2)-Ra-223 (half-life = 11.4 days) is under clinical development is a novel treatment for skeletal metastases from breast and prostate cancer. This article summarizes the current status of preclinical and clinical research on (RaCl2)-Ra-223. Potential advantages of Ra-223 to that of external beam irradiation and registered beta-emitting bone seekers are discussed. Published data of Ra-223 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 for monthly injections of Ra-223 or saline as an adjuvant to external beam radiotherapy. Lastly we present preliminary dose estimates for Ra-223 in humans. results indicate that repeated dosing is feasible and toxicity is low, and that opportunities are available for combined treatment strategies.