RADIATION SAFETY CONSIDERATIONS FOR THE USE OF 223 RaCl2 DE IN MEN WITH CASTRATION- RESISTANT PROSTATE CANCER

The majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride ((RaCl2)-Ra-223), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg(-1) body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered Ra-223 dichloride were typically less than 2 Sv h(-1) MBq(-1) on contact and averaged 0.02 Sv h(-1) MBq(-1) at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5-11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that Ra-223 may provide a new standard of care for patients with CRPC and bone metastases.