Alpha-particle therapy for cancer is an advanced form of targeted radiation treatment that uses alpha-emitting radioactive isotopes to selectively destroy cancer cells. Unlike traditional radiation therapies that often affect both cancerous and healthy tissues, alpha-particle therapy delivers highly potent, localized radiation directly to tumor cells, minimizing damage to surrounding normal cells.
At its core, alpha-particle therapy involves attaching alpha-emitting radionuclides—radioactive atoms that emit alpha particles—to molecules that specifically recognize and bind to cancer cells. These molecules can be antibodies, peptides, or small molecules designed to target unique markers or receptors found predominantly on tumor cells. Once the radioactive compound binds to the cancer cell, the alpha particles it emits travel only a very short distance—typically just a few cell diameters—delivering a powerful burst of energy that causes irreparable double-stranded breaks in the DNA of the cancer cells. This leads to effective cell death while sparing nearby healthy tissue due to the limited range of alpha particles.
Alpha particles themselves are helium nuclei composed of two protons and two neutrons. They have a high linear energy transfer (LET), meaning they deposit a large amount of energy over a very short path. This contrasts with beta particles used in some other radionuclide therapies, which have longer ranges and lower LET, often causing less lethal damage and potentially affecting more surrounding tissue. The high LET of alpha particles makes them especially effective at killing cancer cells, including those that are resistant to other forms of treatment or located in difficult-to-reach areas such as micrometastases—tiny clusters of cancer cells that have spread but are too small to be detected by conventional imaging.
Several alpha-emitting isotopes are used or under investigation in alpha-particle therapy. Radium-223 is one of the most well-known and is approved for treating bone metastases in prostate cancer because it mimics calcium and naturally targets bone tissue. Actinium-225 is another promising isotope, notable for its ability to deliver multiple alpha emissions through its decay chain, enhancing its cancer-killing potential. Bismuth-213, with a shorter half-life, is used in therapies requiring rapid decay and precise timing. These isotopes are linked to targeting molecules through specialized chemical compounds called chelators, which ensure the radioactive atoms remain attached to the targeting agents until they reach the tumor.
One of the key advantages of alpha-particle therapy is its precision. Because alpha particles travel only a few micrometers, the therapy can focus the destructive radiation on cancer cells while sparing normal cells nearby. This precision reduces side effects commonly seen with external beam radiation or chemotherapy, which often affect healthy tissues and cause systemic toxicity. Additionally, alpha-particle therapy can be effective regardless of the oxygenation status of the tumor or the cell cycle phase, unlike some other treatments that rely on oxygen to generate reactive oxygen species for cell killing.
Alpha-particle therapy is part of a broader approach called theranostics, which combines diagnostic imaging and therapy. In theranostics, a radioactive agent first helps identify cancer cells through imaging techniques like PET scans. Once the cancer is located and characterized, a therapeutic version of the agent, loaded with an alpha emitter, is administered to selectively kill the cancer cells. This approach allows doctors to see exactly where the cancer is and monitor how well the treatment is working, enabling personalized and adaptive treatment plans.
Recent clinical developments have shown promising results in using alpha-particle therapy for various cancers, including metastatic prostate cancer, pancreatic cancer, and certain blood cancers. For example, in metastatic castration-resistant prostate cancer, therapies using actinium-225 linked to prostate-specific membrane antigen (PSMA) targeting molecules have demonstrated significant tumor reduction with manageable side effects. In pancreatic cancer, a particularly challenging disease due to its location near critical organs, alpha-particle therapy delivered directly into the tumor has shown potential to provide high-dose, localized radiation in a single session, potentially improving local control while minimizing harm to surrounding tissue
