The only alpha-emitting therapeutic radionuclide in routine clinical use. Radium-223 is a calcium mimetic — incorporated into newly forming bone matrix at sites of osteoblastic activity, concentrating at bone metastases.
Alpha particles:
- Very high linear energy transfer (LET) — causes dense double-strand DNA breaks
- Extremely short path length (~2–10 cell diameters, <100 µm in tissue)
- Minimal dose to adjacent normal marrow compared to beta emitters
- Cannot be imaged with gamma cameras or PET in routine practice (no gamma emission useful for imaging)
ALSYMPCA trial: Ra-223 (6 monthly IV injections) vs placebo in mCRPC with symptomatic bone metastases and no known visceral metastases — overall survival benefit (median 14.9 vs 11.3 months) plus delayed time to first symptomatic skeletal event.
Contraindications: visceral metastases (no soft tissue activity), compromised bone marrow reserve, Crohn’s disease/UC (radium concentrates in gut — GI toxicity risk).
Combination caution: concurrent abiraterone + prednisone + Ra-223 increased fracture risk in the ERA-223 trial — combination requires concomitant bone-protective agents (denosumab or zoledronic acid).
The alpha decay chain of Ra-223 produces 4 alpha particles through 6 short-lived daughters before reaching stable Pb-207.