Alpha particles as radiopharmaceuticals in the treatment of bone metastases: mechanism of action of radium-223 chloride (Alpharadin) and radiation protection.

Approximately 85% to 90% of men with castration-resistant prostate cancer (CRPC) have radiological evidence of bone metastases. To date, however, therapies to manage bone metastases have been primarily palliative. Among CRPC patients with bone metastases, there is a significant unmet need for active antitumor treatment options that are highly efficacious and have a favorable safety profile. This article will present current information about alpha-pharmaceuticals, a new class of targeted cancer therapy for the treatment of patients with CRPC and bone metastases. It will review preclinical and clinical studies of the experimental radiopharmaceutical radium-223 chloride (Alpharadin), a first-in-class, highly targeted and well-tolerated alpha-pharmaceutical under development to improve survival in patients with bone metastases from advanced prostate cancer. Alpharadin kills cancer cells via alpha radiation from the decay of radium-223, a calcium mimetic that naturally self-targets to bone metastases. The mechanism of action of Alpharadin and specifics of administration, radiation protection, and patient management will be discussed.