Fighting prostate cancer with radium-223--not your Madame's isotope.

As each year ushers in new and innovative survivalenhancing treatments for castration-resistant prostate cancer with bone metastases, patients and their physicians have a sense of empowerment associated with this growing therapeutic arsenal.1-5 Nonetheless, nearly 30,000 men still die from prostate cancer every year, and many have debilitating illness from osseous involvement. For this latter group, Alpharadin in Symptomatic Prostate Cancer Patients, a randomized, placebo-controlled study reported by Parker et al. in this issue of the Journal, focuses on a new weapon in anticancer therapy.6 Radium-223 dichloride (radium-223), the first alpha emitter to undergo phase 3 testing and receive approval for clinical use, acts independently of cell cycles, surface markers, and tumor types. The simplicity of the alpha emitter radium-223 lies in its winning combination of a convenient half-life (11.4 days) and its inherent bone-seeking and potent DNA-damaging properties. The authors describe a well-executed international, multicenter trial showing an overall survival benefit associated with radium-223 in more than 900 patients with prostate cancer. The realworld applicability is undeniable; these patients had symptomatic skeletal disease and had received previous or concurrent complementary therapies. No discussion of radium is complete without first acknowledging Madame Marie Curie, who with her husband Pierre first isolated radium-226 from pitchblende. Despite the current widespread availability of radiopharmaceutical agents, shortlived alpha emitters that are suitable for intravenous medical therapy have been limited until recent advances in radiochemical separation and cyclotron-based production of alpha emitters made their generation feasible. Yet, obstacles to their use may still exist. Alpha particles traditionally provoked fear in the lay public and nervousness in the medical community (including some radiation safety officers) because of their enhanced relative biologic effectiveness. The concept of relative biologic effectiveness combines physical linear energy transfers with the radiobiologic effects of ionizing radiation in tissue to provide a medically relevant scale for comparing the potencies of various forms of ionizing radiation. The relative biologic effectiveness of alpha emitters, which is several times that of traditional x-rays (depending on the tissue type), is their most and least attractive feature. Alpha particles are efficient, and they cause cell damage with a single knockout as compared with gamma rays and beta particles. Such killing power is rendered unattractive if it is coupled with an unforgiving half-life. Historically, safety concerns stemmed from the 1601-year half-life of radium-226 and its decay into volatile radon gas. These concerns were further fueled by horror stories that included lost radium sources that underwent accidental heat sterilization and vaporization and closed down entire hospitals.7 However, alpha disintegrations are in fact remarkably easy to shield because of the particles’ heavy mass and limited penetration — picture a minimal-range heavy missile stopped by a sheet of paper. Universal precautions generally suffice. Radium-223 is transportable worldwide in shielded, screw-cap vials. Unlike its older cousin, it rapidly decays into stable compounds — meaning that after several half-lives, one can discard any waste with ordinary trash. Logistically, alpha-emitter