Radium-223
A radioactive form of the mineral radium that behaves like calcium and settles into bone. It gives off very short-range, high-energy particles that damage cancer growing in bone while barely reaching the healthy marrow next to it.
Overview
Radium-223 dichloride (Xofigo) is a calcium mimetic that concentrates in areas of increased bone turnover, such as osteoblastic bone metastases. It decays through a six-stage chain to stable lead-207, emitting predominantly alpha particles (95.3% of emitted energy), with small beta (3.6%) and gamma (1.1%) contributions from itself and its short-lived daughters (polonium-215, lead-211, bismuth-211, thallium-207).
The alpha range is under 100 micrometres in tissue (maximum about 6.2 cm in air), so the dose is deposited within roughly the width of a few cells of the bone surface, largely sparing the adjacent marrow. It was the first alpha-emitting radiopharmaceutical to gain FDA and EMA approval, on the strength of the ALSYMPCA trial's overall-survival benefit in metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral disease.
Ra-223 is obtained from a generator chain rooted in actinium-227 (itself made by neutron irradiation of radium-226 in a reactor); Ac-227 beta-decays to thorium-227, which alpha-decays to Ra-223. Commercial-scale 223Ra is available from Bayer's own supply chain and, more broadly, ORNL, PNNL and Rosatom hold production capability; a 2025 review (the PSI-led 'Alpha Atlas') judged that, unlike most other alpha emitters, 223Ra supply is adequate to global demand and no near-term shortage is expected.
- α (95.3% of emitted energy, range 5-7.5 MeV)
- β− (3.6%, average 0.445 and 0.492 MeV)
- γ (1.1%, 0.01-1.27 MeV range)
Radium-223 was the first alpha-emitting drug ever approved (2013). It homes to bone like calcium and treats prostate cancer that has spread only to bone.
Quadramet (samarium-153 lexidronam) is a radioactive bone-seeking injection that lodges in bone metastases and irradiates them from inside, approved in 1997 to relieve pain from prostate, breast and other cancers spread to bone. Most patients get relief within one to two weeks, but marrow suppression follows at three to five weeks, and radium-223 and PSMA radioligands have largely replaced it.
A radioactive form of strontium is injected into a vein. Because it behaves like calcium, it collects in the damaged, overactive bone around cancer that has spread to bone, and its radiation can relieve bone pain for months.
This paper is a map of the radioactive-cancer-drug field at a pivotal moment, explaining to non-specialists and drug developers alike why these treatments work differently from chemotherapy and what needed to be fixed - supply, dosing science, regulation - before more of them could reach patients.
Radium-223 is an option for symptomatic bone-predominant castration-resistant prostate cancer, now less used since lutetium-PSMA, and should not be combined with abiraterone after the ERA 223 fracture signal.
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