The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer.
The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for 226Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer.
Written by:
Humm JL, Sartor O, Parker C, Bruland OS, Macklis R. Are you the author?
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York; Departments of Medicine and Urology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana; Department of Clinical Oncology, Institute of Cancer Research, Sutton, United Kingdom; Department of Oncology, Norwegian Radium Hospital and Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio.
Reference: Int J Radiat Oncol Biol Phys. 2015 Apr 1;91(5):898-906.
doi: 10.1016/j.ijrobp.2014.12.061
PubMed Abstract
PMID: 25832684