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.

Radium-223 in the Treatment of Osteoblastic Metastases: A Critical Clinical Review

“…For a 70-kg adult, this translates into a patient-injected activity of 3.5 MBq (approximately 95 mCi), which is small in comparison with other radionuclide therapies or even routine diagnostic nuclear medicine procedures. Radiation exposure measurements from patients undergoing 223 RaCl 2 therapy at the 50-kBq/kg group measured at the surface at 0.3 m and 1 m are provided by Dauer et al (14) as shown in Table 1.…”

“…An additional concern is the potential contamination of family members after patient injection. Dauer et al (14) provide useful suggestions to minimize contamination of the family home, which include separating laundry, taking special bathroom provisions, and using gloves to handle body fluids.…”

Ra-223 dichloride management in a Nuclear Medicine Unit: experience of a referral institution

“…Indeed, external exposure to others derived from photon emission from the patient is very low due to attenuation in the patient's body. As assessed by Dauer et al, the estimated dose to a member of the public is expected to be below 1 mSv and below 5 mSv to health care workers [29]. Regarding potential exposure of medical staff, exposure rate constants of Ra-223 is comparable to Tc-99m as assessed by Smith and Stabin, while exposure from patients to others is very low compared to that of Technetium, so that a patient treated with Ra-223 is immediately releasable as per applicable guidelines on patient dose rates [30].…”

Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer

“…a-particles require relatively minimal radiation safety precautions (48). For example, in the average patient receiving 3.5 MBq (95 mCi) of 223 RaCl 2 , the dose measures 0.35 mSv/h (0.035 mrem/h) at 1 m. Thus, no contact precautions are associated with 223 RaCl 2 .…”