title: Radiation safety considerations for the use of ²²³RaCl₂ DE in men with castration-resistant prostate cancer.
abstract: 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 (²²³RaCl₂), 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 ²²³Ra dichloride were typically less than 2 μSv h⁻¹ MBq⁻¹ on contact and averaged 0.02 μSv 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 ²²³Ra may provide a new standard of care for patients with CRPC and bone metastases.
authors.affiliation: *Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY; †Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; ‡Department of Radiology, Weill Cornell Medical College, New York, NY; §Algeta ASA, Oslo, Norway; **Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; ††Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Dauer
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Williamson
authors.forename: John
authors.initials: J
authors.lastname: Humm
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Donoghue
authors.forename: Rashid
authors.initials: R
authors.lastname: Ghani
authors.forename: Robert
authors.initials: R
authors.lastname: Awadallah
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrasquillo
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.forename: Anne-Kirsti
authors.initials: AK
authors.lastname: Aksnes
authors.forename: Colin
authors.initials: C
authors.lastname: Biggin
authors.forename: Vigdis
authors.initials: V
authors.lastname: Reinton
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Jean
authors.initials: J
authors.lastname: St Germain
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000512:Alpha Particles; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D001842:Bone and Bones / Q000473:pathology; D002712:Chlorides / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000532:radiotherapy*; D011835:Radiation Protection / Q000379:methods*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D011883:Radium / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C581106:radium Ra 223 dichloride; D011883:Radium