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.

Fig. 1

An example of radiation safety instructions for patients receiving ²²³Ra dichloride for this clinical Phase 1 study protocol. (Note that specific recommendations may differ based on local regulatory guidance that may differ from one facility or region to another.)

Fig. 2

Whole-body scan showing multiple metastatic disease sites in bone. Images of whole-body scans showing anterior (A) and posterior (B) ^99mTc MDP bone uptake as compared with anterior (C) and posterior (D) ²²³Ra uptake following intravenous injection. Although ²²³Ra images are lower counts and noisier than the bone scan, they clearly show focal accumulation in the most obvious bone metastases: for example, the left scapula and several vertebrae. In addition, excretion into the ascending and transverse colon is noted.