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High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the -Emitter ²²³Ra: Adjuvant or Alternative to Conventional Modalities?

Authors' Affiliations: ¹ Faculty of Medicine, University of Oslo and Department of Oncology, The Norwegian Radium Hospital; ² Algeta ASA, Oslo, Norway; ³ The Karolinska Hospital and Institute, Stockholm, Sweden; and ⁴ Pacific Northwest National Laboratory, Richland, Washington

Requests for reprints: Øyvind S. Bruland, Faculty of Medicine, University of Oslo and Department of Oncology, The Norwegian Radium Hospital, N-0310 Oslo, Norway. Phone: 47-22934000; Fax: 47-22525559; E-mail: oyvind.bruland{at}klinmed.uio.no.

The bone-seeking, -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 ß-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 -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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